Neutron capture therapy: Years of experimentation---Years of reflection

International Nuclear Information System (INIS)

Farr, L.E.

1991-01-01

This report describes early research on neutron capture therapy over a number of years, beginning in 1950, speaking briefly of patient treatments but dwelling mostly on interpretations of our animal experiments. This work carried out over eighteen years, beginning over forty years ago. Yet, it is only fitting to start by relating how neutron capture therapy became part of Brookhaven's Medical Research Center program

New compounds for neutron capture therapy (NCT) and their significance

International Nuclear Information System (INIS)

Fairchild, R.G.; Bond, V.P.

1982-01-01

Clearly the most effective tumor therapy would be obtained by the selective targeting of cytotoxic agents to tumor cells. Although many biomolecules are known to be taken up in tumors, the targeting of cytotoxic agents to tumors is limited by the fact that other essential cell pools compete with equal or even greater effectiveness. The approach of delivering stable non-toxic isotopes to tumor, with activation by means of an external radiation beam, is advantageous for two reasons: (1) it obviates problems associated with high uptake of isotopes in normal tissues, as these cell pools can be excluded from the radiation field, and (2) the general tumor area can be included in the activating beam field; thus, the possibility exists that all microscopic tumor extensions can be irradiated. As long as range of reaction products is short, dose will be restricted to the tumor, with a resultant high therapeutic ratio. This method can be accomplished with either photon activation therapy (PAT) or Neutron Capture Therapy (NCT), the latter will be emphasized here. The range of the high LET, low OER particles from the 10 B(n,α) 7 Li reaction is approx. 10 μm, or one cell diameter; hence this reaction is optimal for cell killing. A number of biomolecules have been investigated as possible vehicles for transport of boron to tumors, including phenothiazines, thiouracils, porphyrins, nucleosides, and amino acids. Biodistributions of these compounds show selective concentration in tumor adequate for therapy. The biological halflives are in the order of days, allowing the possibility of fractionated or protracted irradiations. The radiobiological and physical implication of these parameters on NCT are discussed. The possibility of using an approximately-monoenergetic, scandium-filtered beam of about 2 keV, to reduce the dose from background radiations by about 85%, is also discussed

Current status of neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-05-01

There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT.

Current status of neutron capture therapy

International Nuclear Information System (INIS)

2001-05-01

There are about 6000 new glioblastoma multiform brain tumours diagnosed each year in the United States of America alone. This cancer is usually fatal within six months of diagnosis even with current standard treatments. Research on boron neutron capture therapy (BNCT) has been considered as a method of potentially curing such cancers. There is a great interest at under-utilised research reactors institutions to identify new medical utilization, attractive to the general public. Neutron capture therapy is a true multidisciplinary topic with a large variety of individuals involved. This publication attempts to provide current information for all those thinking about being involved with NCT, based on the knowledge and experience of those who have pioneered the treatment. It covers the whole range of NCT from designing reactor conversions or new facilities, through to clinical trials and their effectiveness. However, since most work has been done with boron capture therapy for brain tumours using modified thermal research reactors, this tends to be the focus of the report. One of the factors which need to be addressed at the beginning is the timing of the further development of NCT facilities. It should be emphasised that all current work is still at the research stage. Many of those now involved believe that there is little need for many more research facilities until such time as the treatment shows more promising results. For this and other reasons discussed in the report, very serious consideration should be given by research reactor owners and operators before spending large sums of money converting their facilities for NCT

Microdosimetry for Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Maughan, R.L.; Kota, C.

2000-01-01

The specific aims of the research proposal were as follows: (1) To design and construct small volume tissue equivalent proportional counters for the dosimetry and microdosimetry of high intensity thermal and epithermal neutron beams used in BNCT, and of modified fast neutron beams designed for boron neutron capture enhanced fast neutron therapy (BNCEFNT). (2) To develop analytical methods for estimating the biological effectiveness of the absorbed dose in BNCT and BNCEFNT based on the measured microdosimetric spectra. (3) To develop an analytical framework for comparing the biological effectiveness of different epithermal neutron beams used in BNCT and BNCEFNT, based on correlated sets of measured microdosimetric spectra and radiobiological data. Specific aims (1) and (2) were achieved in their entirety and are comprehensively documented in Jay Burmeister's Ph.D. dissertation entitled ''Specification of physical and biologically effective absorbed dose in radiation therapies utilizing the boron neutron capture reaction'' (Wayne State University, 1999). Specific aim (3) proved difficult to accomplish because of a lack of sufficient radiobiological data

Neutron capture therapy for melanoma

Energy Technology Data Exchange (ETDEWEB)

Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

1988-01-01

The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs.

Neutron capture therapy for melanoma

International Nuclear Information System (INIS)

Coderre, J.A.; Glass, J.D.; Micca, P.; Fairchild, R.G.

1988-01-01

The development of boron-containing compounds which localize selectively in tumor may require a tumor-by-tumor type of approach that exploits any metabolic pathways unique to the particular type of tumor. Melanin-producing melanomas actively transport and metabolize aromatic amino acids for use as precursors in the synthesis of the pigment melanin. It has been shown that the boron-containing amino acid analog p-borono-phenylalanine (BPA) is selectively accumulated in melanoma tissue, producing boron concentrations in tumor that are within the range estimated to be necessary for successful boron neutron capture therapy (BNCT). We report here the results of therapy experiments carried out at the Brookhaven Medical Research Reactor (BMRR). 21 refs., 5 figs., 3 tabs

Investigation of boron conjugated thiouracil derivates for neutron capture therapy of melanoma

International Nuclear Information System (INIS)

Corderoy-Buck, S.; Allen, B.J.; Wilson, J.G.; Tjarks, W.; Gabel, D.; Barkla, D.; Patwardhan, A.; Chandler, A.; Moore, D.E.

1990-01-01

Boron conjugated thiouracil derivatives were investigated as possible agents for boron neutron capture therapy (BNCT) of melanoma. Nude mice bearing human or murine melanoma xenografts were used for biodistribution studies following i.p. or i.t. (intratumoural) injection of these drugs. Boron content was analysed by inductively coupled plasma atomic emission spectrometry. Wide variation between tumour lines was observed with respect to accumulation of these drugs, but they appear to offer potential as melanoma affined boron carriers if solubility problems are overcome by liposome entrapment. Pre-treatment to stimulate melanogenesis may also prove a useful adjunct in achieving the therapeutic concentrations of boron necessary for successful BNCT. 25 refs., 4 tabs., 3 figs

Accelerator based neutron source for neutron capture therapy

International Nuclear Information System (INIS)

Salimov, R.; Bayanov, B.; Belchenko, Yu.; Belov, V.; Davydenko, V.; Donin, A.; Dranichnikov, A.; Ivanov, A.; Kandaurov, I; Kraynov, G.; Krivenko, A.; Kudryavtsev, A.; Kursanov, N.; Savkin, V.; Shirokov, V.; Sorokin, I.; Taskaev, S.; Tiunov, M.

2004-01-01

Full text: The Budker Institute of Nuclear Physics (Novosibirsk) and the Institute of Physics and Power Engineering (Obninsk) have proposed an accelerator based neutron source for neutron capture and fast neutron therapy for hospital. Innovative approach is based upon vacuum insulation tandem accelerator (VITA) and near threshold 7 Li(p,n) 7 Be neutron generation. Pilot accelerator based neutron source for neutron capture therapy is under construction now at the Budker Institute of Nuclear Physics, Novosibirsk, Russia. In the present report, the pilot facility design is presented and discussed. Design features of facility components are discussed. Results of experiments and simulations are presented. Complete experimental tests are planned by the end of the year 2005

Gadolinium atom on neutron capture therapy

International Nuclear Information System (INIS)

Oda, Y.; Takagaki, M.; Miyatake, S.; Kikuchi, H.

1994-01-01

This report describes our measurements of gadolinium concentrations in several brain tumors obtained from fresh surgical specimens, as compared with corresponding concentrations in the blood. Moreover we tried to find out if the gadolinium concentration is high enough to use this compound in the treatment of brain tumors by neutron capture therapy. (J.P.N.)

Advances in neutron capture therapy 2006. Proceedings of 12th international congress on neutron capture therapy

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Kobayashi, Tooru; Fukuda, Hiroshi

2006-01-01

The Twelfth International Congress on Neutron Capture Therapy (ICNCT-12) is being held from October 9th to 13th, 2006 at the Kagawa International Congress Hall in Takamatsu, Kagawa, Japan. The main theme of the congress is From the past to the Future'. Five symposiums were organized to accommodate all the contributions from the international scientific committees of the International Society for Neutron Capture Therapy (ISNCT), and two symposiums were added to balance the number of fields of specialties. The seven symposiums for ICNCT-12 are as follows: 1) Clinical Results of BNCT for Brain Tumors, 2) Dosimetry, 3) Treatment Planning system, 4) Drug Delivery System, 5) Biomedical and General Matters, 6) BNCT Systems using Accelerators, 7) New Applications and Protocols for BNCT. There are a total of 195 presentations in this congress: 3 special lectures, 34 symposium presentations, 10 presentations in two special sessions from the recipients of the Ralph G. Fairchild Award, 70 presentations in the oral parallel sessions and 78 presentations in the poster sessions. A compilation of 169 papers are published in this proceedings. The 165 of the presented papers are indexed individually. (J.P.N.)

Clinical considerations for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Madoc-Jones, H.; Wazer, D.E.; Zamenhof, R.G.; Harling, O.K.; Bernard, J.A. Jr.

1990-01-01

The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the US in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should not be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam cases gamma rays to be generated when it interacts with tissue, they think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue

Neutron capture therapy with thermal neutrons at IRT MIFI

International Nuclear Information System (INIS)

Zajtsev, K.N.; Portnov, A.A.; Savkin, V.A.; Kulakov, V.N.; Khokhlov, V.F.; Shejno, I.N.; Vajnson, A.A.; Kozlovskaya, N.G.; Meshcherikova, V.V.; Mitin, V.N.; Yarmonenko, S.P.

2001-01-01

Combined preclinical investigations into neutron capture therapy are conducted. Malignant melanoma was adopted as the line of investigation; boron-containing and gadolinium-containing preparations were used during the neutron capture therapy working off. Preparations produce secondary varying radiations when used in tumor. Dogs with spontaneous melanoma were used for the experiments. Procedures for the irradiation of dogs by neutron beam as the stage before use for the treatment of oncology patients were finished off; efficiency of neutron beam influence on normal tissues during the irradiation of dogs with melanoma (and without it) in antitumor and side effect sense was estimated [ru

General considerations for neutron capture therapy at a reactor facility

International Nuclear Information System (INIS)

Binney, S.E.

2001-01-01

In addition to neutron beam intensity and quality, there are also a number of other significant criteria related to a nuclear reactor that contribute to a successful neutron capture therapy (NCT) facility. These criteria are classified into four main categories: Nuclear design factors, facility management and operations factors, facility resources, and non-technical factors. Important factors to consider are given for each of these categories. In addition to an adequate neutron beam intensity and quality, key requirements for a successful neutron capture therapy facility include necessary finances to construct or convert a facility for NCT, a capable medical staff to perform the NCT, and the administrative support for the facility. The absence of any one of these four factors seriously jeopardizes the overall probability of success of the facility. Thus nuclear reactor facility management considering becoming involved in neutron capture therapy, should it be proven clinically successful, should take all these factors into consideration. (author)

Neutron spectrum for neutron capture therapy in boron

International Nuclear Information System (INIS)

Medina C, D.; Soto B, T. G.; Baltazar R, A.; Vega C, H. R.

2016-10-01

Glioblastoma multiforme is the most common and aggressive of brain tumors and is difficult to treat by surgery, chemotherapy or conventional radiation therapy. One treatment alternative is the Neutron Capture Therapy in Boron, which requires a beam modulated in neutron energy and a drug with 10 B able to be fixed in the tumor. When the patients head is exposed to the neutron beam, they are captured by the 10 B and produce a nucleus of 7 Li and an alpha particle whose energy is deposited in the cancer cells causing it to be destroyed without damaging the normal tissue. One of the problems associated with this therapy is to have an epithermal neutrons flux of the order of 10 9 n/cm 2 -sec, whereby irradiation channels of a nuclear research reactor are used. In this work using Monte Carlo methods, the neutron spectra obtained in the radial irradiation channel of the TRIGA Mark III reactor are calculated when inserting filters whose position and thickness have been modified. From the arrangements studied, we found that the Fe-Cd-Al-Cd polyethylene filter yielded a ratio between thermal and epithermal neutron fluxes of 0.006 that exceeded the recommended value (<0.05), and the dose due to the capture gamma rays is lower than the dose obtained with the other arrangements studied. (Author)

Prophylaxis and Therapy Against Chemical Agents

Science.gov (United States)

2009-11-01

Hematopoietic Consequences F. Dorandeu 5) pH Dependent Toxicity of Sulphur Mustard In Vitro J. Mikler Nerve Agents / Scavengers 1) Mutagenesis...symptoms such as salivation or shortness of breath and lower level exposures could be rendered inconsequential. B.2 CURRENT THERAPY FOR NERVE AGENT

Role of gel dosimeters in boron neutron capture therapy

International Nuclear Information System (INIS)

Khajeali, Azim; Farajollahi, Ali Reza; Khodadadi, Roghayeh; Kasesaz, Yaser; Khalili, Assef

2015-01-01

Gel dosimeters have acquired a unique status in radiotherapy, especially with the advent of the new techniques in which there is a need for three-dimensional dose measurement with high spatial resolution. One of the techniques in which the use of gel dosimeters has drawn the attention of the researchers is the boron neutron capture therapy. Exploring the history of gel dosimeters, this paper sets out to study their role in the boron neutron capture therapy dosimetric process. - Highlights: • Gel dosimeters have been investigated. • Conventional dosimetric proses of BNCT has been investigated. • Role of gel dosimeters in BNCT has been investigated

Anesthetic management of Boron Neutron Capture Therapy for glioblastoma

International Nuclear Information System (INIS)

Shinomura, T.; Furutani, H.; Osawa, M.; Ono, K.; Fukuda, K.

2000-01-01

General anesthesia was given to twenty-seven patients who received Boron Neutron Capture Therapy (BNCT) under craniotomy at Kyoto University Research Reactor from 1991 to 1999. Special considerations are required for anesthesia. (author)

Boron microquantification in oral mucosa and skin following administration of a neutron capture therapy agent

International Nuclear Information System (INIS)

Kiger, S.W. III; Micca, P.L.; Morris, G.M.; Coderre, J.A.

2002-01-01

Clinical trials of boron neutron capture therapy (BNCT) for intracranial tumours using boronphenylalanine-fructose undertaken at Harvard-MIT and Brookhaven National Laboratory have observed acute normal tissue reactions in the skin and oral mucosa. Because the range of the 10 B(n,a) 7 Li reaction products is very short, 10-14 μm combined, knowledge of the 10B microdistribution in tissue is critical for understanding the microdosimetry and radiobiology of BNCT. This paper reports measurements of the microdistribution of 10 B in an animal model, rat skin and tongue, using high resolution quantitative autoradiography (HRQAR), a neutron-induced track etch autoradiographic technique. The steep spatial gradient and high absolute value relative to blood of the 10 B concentration observed in some strata of the rat tongue epithelium and skin are important for properly evaluating the radiobiology and the biological effectiveness factors for normal tissue reactions such as oral mucositis, which are generally assessed using the blood boron concentration rather than the tissue boron concentration. (author)

Dosimetry and stability studies of the boron neutron capture therapy agent F-BPA-Fr using PET and MRI

Science.gov (United States)

Dyke, Jonathan Paul

The treatment of deep seated brain tumors such as glioblastoma Multiforme has been unsuccessful for many patients. Surgical debulking, chemotherapy and standard radiotherapy have met with limited success. Boron neutron capture therapy offers a binary mode brachytherapy based on the following capture reaction that may provide an innovative alternative to standard forms of treatment:10B + n /to/ 11B /to 7Li + 4He + 2.31 MeVBoron is chemically attached to a tumor binding compound creating a non-toxic neutron absorber. A dose of epithermal neutrons provides the catalyst to produce the lithium and alpha particles which destroy any tissue within a length of one cell diameter from the boron compound. This dissertation uses 19F-MRI and 18F-PET to provide answers to the localization and biodistribution questions that arise in such a treatment modality. Practical patient dosimetry and actual treatment planning using the PET data is also examined. Finally, theoretical work done in the areas of compartmental modelling dealing with pharmacokinetic uptake of the PET radiotracer and dose analysis in microdosimetry is also presented.

Boron containing compounds and their preparation and use in neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Gabel, D.

1992-09-01

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

Boron neutron capture therapy of ocular melanoma and intracranial glioma using p-boronophenylalanine

International Nuclear Information System (INIS)

Coderre, J.A.; Greenberg, D.; Micca, P.L.; Joel, D.D.; Saraf, S.; Packer, S.

1990-01-01

During conventional radiotherapy, the dose that can be delivered to the tumor is limited by the tolerance of the surrounding normal tissue within the treatment volume. Boron Neutron Capture Therapy (BNCT) represents a promising modality for selective tumor irradiation. The key to effective BNCT is selective localization of 10 B in the tumor. We have shown that the synthetic amino acid p-boronophenylalanine (BPA) will selectively deliver boron to melanomas and other tumors such as gliosarcomas and mammary carcinomas. Systemically delivered BPA may have general utility as a boron delivery agent for BNCT. In this paper, BNCT with BPA is used in treatment of experimentally induced gliosarcoma in rats and nonpigmented melanoma in rabbits. The tissue distribution of boron is described, as is response to the BNCT. 6 refs., 4 figs., 1 tab

Organic molecule-based photothermal agents: an expanding photothermal therapy universe.

Science.gov (United States)

Jung, Hyo Sung; Verwilst, Peter; Sharma, Amit; Shin, Jinwoo; Sessler, Jonathan L; Kim, Jong Seung

2018-04-03

Over the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials. In this tutorial review, we provide a structured description of the main classes of organic photothermal agents and their characteristics. Representative agents that have been studied in the context of photothermal therapy since 2000 are summarized and recent advances in using PTT agents to address various cancers indications are highlighted.

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Zamenhof, R.G.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Clement, S.D.; Harling, O.K.; Yanch, J.C.

1990-01-01

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated

Neutron dosimetry in boron neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Miola, U.J.; Ettinger, K.V.

1981-01-01

The recent development of various borated compounds and the utilization of one of these (Na 2 B 12 H 11 SH) to treat brain tumors in clinical studies in Japan has renewed interest in neutron capture therapy. In these procedures thermal neutrons interact with 10 B in boron containing cells through the 10 B(n,α) 7 Li reaction producing charged particles with a maximum range of approx. 10μm in tissue. Borated analogs of chlorpromazine, porphyrin, thiouracil and deoxyuridine promise improved tumor uptake and blood clearance. The therapy beam from the Medical Research Reactor in Brookhaven contains neutrons from a modified and filtered fission spectrum and dosimetric consequences of the use of the above mentioned compounds in conjunction with thermal and epithermal fluxes are discussed in the paper. One of the important problems of radiation dosimetry in capture therapy is determination of the flux profile and, hence, the dose profile in the brain. This has been achieved by constructing a brain phantom made of TE plastic. The lyoluminescence technique provides a convenient way of monitoring the neutron flux distributions; the detectors for this purpose utilize 6 Li and 10 B compounds. Such compounds have been synthesized specially for the purpose of dosimetry of thermal and epithermal beams. In addition, standard lyoluminescent phosphors, like glutamine, could be used to determine the collisional component of the dose as well as the contribution of the 14 N(n,p) 14 C reaction. Measurements of thermal flux were compared with calculations and with measurements done with activation foils

New carbon-carbon linked amphiphilic carboranyl-porphyrins as boron neutron capture agents

International Nuclear Information System (INIS)

Vicente, M.G.H.; Wickramasinghe, A.; Shetty, S.J.; Smith, K.M.

2000-01-01

Novel amphiphilic carboranyl-porphyrins have been synthesized for Boron Neutron Capture Therapy (BNCT). These compounds have carbon-carbon bonds between the carborane residues and the porphyrin meso-phenyl groups, and contain 28-31% boron by weight . (author)

Beta-Blocking Agents and Electroconvulsive Therapy

NARCIS (Netherlands)

W.W. van den Broek (Walter); T.H.N. Groenland (Theo); A. Kusuma (Ari); T.K. Birkenhäger (Tom); E.M. Pluijms (Esther); J.A. Bruijn (Jan); P.G.H. Mulder (Paul)

2007-01-01

textabstractIn this review we want to summarize the results of the placebo-controlled randomized clinical trials with betablocking adrenergic agents during electroconvulsive therapy (ECT), and review the effect on seizure duration and cardiovascular variables. We searched for studies in the

Carborane derivative development for boron neutron capture therapy. Final report

International Nuclear Information System (INIS)

Barnum, Beverly A.; Yan Hao; Moore, Roger; Hawthorne, M. Frederick; Baum, Kurt

1999-01-01

Boron Neutron Capture Therapy [BNCT] is a binary method of cancer therapy based on the capture of neutrons by a boron-10 atom [ 10 B]. Cytotoxic 7 Li nuclei and α-particles are emitted, with a range in tissue of 9 and 5 microm, respectively, about one cell diameter. The major obstacle to clinically viable BNCT is the selective localization of 5-30 ppm 10 B in tumor cells required for effective therapy. A promising approach to BNCT is based on hydrophilic boron-rich oligomeric phosphate diesters, or ''trailers'' that have been shown to concentrate selectively in tumor tissue. Examples of these compounds were prepared previously at high cost using an automated DNA synthesizer. Direct synthesis methods are needed for the production of gram-scale quantities for further biological evaluation. The work accomplished as a result of the collaboration between Fluorochem, Inc. and UCLA demonstrates that short oligomers containing at least five carborane units with four phosphodiester linkages can be prepared in substantial quantities. This work was accomplished by the application of standard phosphoramidite coupling chemistry

Commissioning of accelerator based boron neutron capture therapy system

International Nuclear Information System (INIS)

Nakamura, S.; Wakita, A.; Okamoto, H.; Igaki, H.; Itami, J.; Ito, M.; Abe, Y.; Imahori, Y.

2017-01-01

Boron neutron capture therapy (BNCT) is a treatment method using a nuclear reaction of 10 B(n, α) 7 Li. BNCT can be deposited the energy to a tumor since the 10 B which has a higher cross-section to a neutron is high is concentrated on the tumor. It is different from conventional radiation therapies that BNCT expects higher treatment effect to radiation resistant tumors since the generated alpha and lithium particles have higher radiological biological effectiveness. In general, BNCT has been performed in research nuclear reactor. Thus, BNCT is not widely applied in a clinical use. According to recent development of accelerator-based boron neutron capture therapy system, the system has an adequate flux of neutrons. Therefore, National Cancer Canter Hospital, Tokyo, Japan is planning to install accelerator based BNCT system. Protons with 2.5 MeV are irradiated to a lithium target system to generate neutrons. As a result, thermal load of the target is 50 kW since current of the protons is 20.0 mA. Additionally, when the accelerator-based BNCT system is installed in a hospital, the facility size is disadvantage in term of neutron measurements. Therefore, the commissioning of the BNCT system is being performed carefully. In this article, we report about the commissioning. (author)

Phantom experiment of depth-dose distributions for gadolinium neutron capture therapy

International Nuclear Information System (INIS)

Matsumoto, T.; Kato, K.; Sakuma, Y.; Tsuruno, A.; Matsubayashi, M.

1993-01-01

Depth-dose distributions in a tumor simulated phantom were measured for thermal neutron flux, capture gamma-ray and internal conversion electron dose rates for gadolinium neutron capture therapy. The results show that (i) a significant dose enhancement can be achieved in the tumor by capture gamma-rays and internal conversion electrons but the dose is mainly due to capture gamma-rays from the Gd(n, γ) reactions, therefore, is not selective at the cellular level, (ii) the dose distribution was a function of strongly interrelated parameters such as gadolinium concentrations, tumor site and neutron beam size (collimator aperture size), and (iii) the Gd-NCT by thermal neutrons appears to be a potential for treatment of superficial tumor. (author)

Design of a boron neutron capture enhanced fast neutron therapy assembly

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhonglu [Georgia Inst. of Technology, Atlanta, GA (United States)

2006-12-01

The use of boron neutron capture to boost tumor dose in fast neutron therapy has been investigated at several fast neutron therapy centers worldwide. This treatment is termed boron neutron capture enhanced fast neutron therapy (BNCEFNT). It is a combination of boron neutron capture therapy (BNCT) and fast neutron therapy (FNT). It is believed that BNCEFNT may be useful in the treatment of some radioresistant brain tumors, such as glioblastoma multiform (GBM). A boron neutron capture enhanced fast neutron therapy assembly has been designed for the Fermilab Neutron Therapy Facility (NTF). This assembly uses a tungsten filter and collimator near the patient's head, with a graphite reflector surrounding the head to significantly increase the dose due to boron neutron capture reactions. The assembly was designed using Monte Carlo radiation transport code MCNP version 5 for a standard 20x20 cm² treatment beam. The calculated boron dose enhancement at 5.7-cm depth in a water-filled head phantom in the assembly with a 5x5 cm² collimation was 21.9% per 100-ppm ¹⁰B for a 5.0-cm tungsten filter and 29.8% for a 8.5-cm tungsten filter. The corresponding dose rate for the 5.0-cm and 8.5-cm thick filters were 0.221 and 0.127 Gy/min, respectively; about 48.5% and 27.9% of the dose rate of the standard 10x10 cm² fast neutron treatment beam. To validate the design calculations, a simplified BNCEFNT assembly was built using four lead bricks to form a 5x5 cm² collimator. Five 1.0-cm thick 20x20 cm² tungsten plates were used to obtain different filter thicknesses and graphite bricks/blocks were used to form a reflector. Measurements of the dose enhancement of the simplified assembly in a water-filled head phantom were performed using a pair of tissue-equivalent ion chambers. One of the ion chambers is loaded with 1000-ppm natural boron (184-ppm ¹⁰B) to measure dose due to boron neutron capture. The

Degradation of Akt using protein-catalyzed capture agents.

Science.gov (United States)

Henning, Ryan K; Varghese, Joseph O; Das, Samir; Nag, Arundhati; Tang, Grace; Tang, Kevin; Sutherland, Alexander M; Heath, James R

2016-04-01

Abnormal signaling of the protein kinase Akt has been shown to contribute to human diseases such as diabetes and cancer, but Akt has proven to be a challenging target for drugging. Using iterative in situ click chemistry, we recently developed multiple protein-catalyzed capture (PCC) agents that allosterically modulate Akt enzymatic activity in a protein-based assay. Here, we utilize similar PCCs to exploit endogenous protein degradation pathways. We use the modularity of the anti-Akt PCCs to prepare proteolysis targeting chimeric molecules that are shown to promote the rapid degradation of Akt in live cancer cells. These novel proteolysis targeting chimeric molecules demonstrate that the epitope targeting selectivity of PCCs can be coupled with non-traditional drugging moieties to inhibit challenging targets. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Neutron capture therapy

International Nuclear Information System (INIS)

Jun, B. J.

1998-11-01

The overall state of the art related with neutron capture therapy(NCT) is surveyed. Since the field related with NCT is very wide, it is not intended to survey all related subjects in depth. The primary objective of this report is to help those working for the installation of a NCT facility and a PGNAA(prompt gamma ray neutron activation analysis) system for the boron analysis understand overall NCT at Hanaro. Therefore, while the parts of reactor neutron source and PGNAA are dealt in detail, other parts are limited to the level necessary to understand related fields. For example, the subject of chemical compound which requires intensive knowledge on chemistry, is not dealt as a separated item. However, the requirement of a compound for NCT, currently available compounds, their characteristics, etc. could be understood through this report. Although the subject of cancer treated by NCT is out of the capability of the author, it is dealt focussing its characteristics related with the success of NCT. Each detailed subject is expected to be dealt more detail by specialists in future. This report would be helpful for the researchers working for the NCT to understand related fields. (author). 128 refs., 3 tabs., 12 figs

Recent advances in neutron capture therapy (NCT)

International Nuclear Information System (INIS)

Fairchild, R.G.

1985-01-01

The application of the 10 B(n,α) 7 Li reaction to cancer radiotherapy (Neutron Capture therapy, or NCT) has intrigued investigators since the discovery of the neutron. This paper briefly summarizes data describing recently developed boronated compounds with evident tumor specificity and extended biological half-lives. The implication of these compounds to NCT is evaluated in terms of Therapeutic Gain (TG). The optimization of NCT using band-pass filtered beams is described, again in terms of TG, and irradiation times with these less intense beams are estimated. 24 refs., 3 figs., 3 tabs

{sup 1}H and {sup 10}B NMR and MRI investigation of boron- and gadolinium-boron compounds in boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Bonora, M., E-mail: marco.bonora@unipv.it [Physics Department ' A. Volta' , University of Pavia, Via Bassi 6, 27100 Pavia (Italy)] [CNISM Unit (Italy); Corti, M.; Borsa, F. [Physics Department ' A. Volta' , University of Pavia, Via Bassi 6, 27100 Pavia (Italy)] [CNISM Unit (Italy); Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S. [Nuclear and Theoretical Physics Department, University of Pavia, Via Bassi 6, 27100 Pavia (Italy)] [INFN Pavia (Italy); Zonta, C.; Clerici, A.M.; Cansolino, L.; Ferrari, C.; Dionigi, P. [Surgical Sciences Department, Experimental Surgery Laboratory, University of Pavia, Pavia (Italy); Porta, A.; Zanoni, G.; Vidari, G. [Organic Chemistry Department, University of Pavia, Via Taramelli 10, 27100 Pavia (Italy)

2011-12-15

{sup 10}B molecular compounds suitable for Boron Neutron Capture Therapy (BNCT) are tagged with a Gd(III) paramagnetic ion. The newly synthesized molecule, Gd-BPA, is investigated as contrast agent in Magnetic Resonance Imaging (MRI) with the final aim of mapping the boron distribution in tissues. Preliminary Nuclear Magnetic Resonance (NMR) measurements, which include {sup 1}H and {sup 10}B relaxometry in animal tissues, proton relaxivity of the paramagnetic Gd-BPA molecule in water and its absorption in tumoral living cells, are reported.

Workshop on neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Fairchild, R.G.; Bond, V.P. (eds.)

1986-01-01

Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed to be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior.

Workshop on neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Bond, V.P.

1986-01-01

Potentially optimal conditions for Neutron Capture Therapy (NCT) may soon be in hand due to the anticipated development of band-pass filtered beams relatively free of fast neutron contaminations, and of broadly applicable biomolecules for boron transport such as porphyrins and monoclonal antibodies. Consequently, a number of groups in the US are now devoting their efforts to exploring NCT for clinical application. The purpose of this Workshop was to bring these groups together to exchange views on significant problems of mutual interest, and to assure a unified and effective approach to the solutions. Several areas of preclinical investigation were deemed to be necessary before it would be possible to initiate clinical studies. As neither the monomer nor the dimer of sulfhydryl boron hydride is unequivocally preferable at this time, studies on both compounds should be continued until one is proven superior

Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety.

Science.gov (United States)

Al-Mayouf, Sulaiman M; Alenazi, Abdullatif; AlJasser, Hind

2016-06-01

To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period. In all, 134 children (89 female) with various rheumatic diseases were treated with biologic agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus (12.7%) and vasculitis (4.5%). All patients received concomitant therapy (corticosteroids and disease-modifying antirheumatic drugs). In total, 273 treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47 adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept). Therapy was switched to another agent in 57 (42.5%) patients, mainly because of inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events were notified; of these, the most frequent were infusion-related reactions (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One patient developed macrophage activation syndrome. Biologic agents were used in children with a range of rheumatic diseases. Of these, the most frequent was JIA. Off-label use of biologic agents in our cohort is common. These agents seem safe. However, they may associated with various adverse events. Sequential therapy seems well tolerated. However, this should be carefully balanced and considered on an individual basis. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Medical and biological requirements for boron neutron capture therapy

International Nuclear Information System (INIS)

Gahbauer, R.; Goodman, J.H.; Kanellitsas, C.; Clendenon, N.; Blue, J.

1986-01-01

In conventional radiation therapy, tumor doses applied to most solid tumors are limited by the tolerance of normal tissues. The promise of Boron Neutron Capture Therapy lies in its potential to deposit high doses of radiation very specifically to tumor tissue. Theoretically ratios of tumor to normal tissue doses can be achieved significantly higher than conventional radiotherapeutic techniques would allow. Effective dose distributions obtainable are a complex function of the neutron beam characteristics and the macro and micro distributions of boron in tumor and normal tissues. Effective RBE doses are calculated in tumors and normal tissue for thermal, epithermal and 2 keV neutrons

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer

Energy Technology Data Exchange (ETDEWEB)

Haapaniemi, Aaro, E-mail: aaro.haapaniemi@hus.fi [Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Kankaanranta, Leena [Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Saat, Riste [Department of Radiology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Koivunoro, Hanna; Saarilahti, Kauko [Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Mäkitie, Antti; Atula, Timo [Department of Otorhinolaryngology–Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki (Finland); Joensuu, Heikki [Department of Oncology, Helsinki University Hospital and University of Helsinki, Helsinki (Finland)

2016-05-01

Purpose: To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. Methods and Materials: Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. Results: Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. Conclusions: Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.

Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch

International Nuclear Information System (INIS)

Monti Hughes, A.; Pozzi, E.C.C.; Thorp, S.

2013-01-01

Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of BNCT mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer and pre cancer model. Despite therapeutic efficacy, mucositis induced in premalignant tissue was dose limiting and favored, in some cases, tumor development. In a clinical scenario, oral mucositis limits the dose administered to head and neck tumors. Aim: Our aim was to evaluate the effect of the administration of different radioprotective agents, seeking to reduce BNCT-induced mucositis to acceptable levels in dose-limiting premalignant tissue; without compromising therapeutic effect evaluated as inhibition on tumor development in premalignant tissue; without systemic or local side effects; and without negative effects on the biodistribution of the boron compound used for treatment. Materials and methods: Cancerized hamsters with DMBA (dimethylbenzanthracene) were treated with BPA-BNCT 5 Gy total absorbed dose to premalignant tissue, at the RA-3 Nuclear Reactor, divided into different groups: 1-treated with FLUNIXIN; 2- ATORVASTATIN; 3-THALIDOMIDE; 4-HISTAMINE (two concentrations: Low -1 mg/ml- and High -5 mg/ml-); 5-JNJ7777120; 6-JNJ10191584; 7-SALINE (vehicle). Cancerized animals without any treatment (neither BNCT nor radioprotective therapy) were also analyzed. We followed the animals during one month and evaluated the percentage of animals with unacceptable/severe mucositis, clinical status and percentage of animals with new tumors post treatment. We also performed a preliminary biodistribution study of BPA + Histamine “low” concentration to evaluate the potential effect of the radioprotector on BPA biodistribution. Results: Histamine �

Neutron therapy coupling brachytherapy and boron neutron capture therapy (BNCT) techniques

International Nuclear Information System (INIS)

Chaves, Iara Ferreira.

1994-12-01

In the present dissertation, neutron radiation techniques applied into organs of the human body are investigated as oncologic radiation therapy. The proposal treatment consists on connecting two distinct techniques: Boron Neutron Capture Therapy (BNCT) and irradiation by discrete sources of neutrons, through the brachytherapy conception. Biological and radio-dosimetrical aspects of the two techniques are considered. Nuclear aspects are discussed, presenting the nuclear reactions occurred in tumoral region, and describing the forms of evaluating the dose curves. Methods for estimating radiation transmission are reviewed through the solution of the neutron transport equation, Monte Carlo methodology, and simplified analytical calculation based on diffusion equation and numerical integration. The last is computational developed and presented as a quickly way to neutron transport evaluation in homogeneous medium. The computational evaluation of the doses for distinct hypothetical situations is presented, applying the coupled techniques BNTC and brachytherapy as an possible oncologic treatment. (author). 78 refs., 61 figs., 21 tabs

Proceedings of the first international symposium on neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Fairchild, R.G.; Brownell, G.L. (eds.)

1982-01-01

This meeting was arranged jointly by MIT and BNL in order to illuminate progress in the synthesis and targeting of boron compounds and to evaluate and document progress in radiobiological and dosimetric aspects of neutron capture therapy. It is hoped that this meeting will facilitate transfer of information between groups working in these fields, and encourage synergistic collaboration.

Proceedings of the first international symposium on neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Brownell, G.L.

1982-01-01

This meeting was arranged jointly by MIT and BNL in order to illuminate progress in the synthesis and targeting of boron compounds and to evaluate and document progress in radiobiological and dosimetric aspects of neutron capture therapy. It is hoped that this meeting will facilitate transfer of information between groups working in these fields, and encourage synergistic collaboration

Recombination methods for boron neutron capture therapy dosimetry

International Nuclear Information System (INIS)

Golnik, N.; Tulik, P.; Zielczynski, M.

2003-01-01

The radiation effects of boron neutron capture therapy (BNCT) are associated with four-dose-compartment radiation field - boron dose (from 10 B(n,α) 7 Li) reaction), proton dose from 14 N(n,p) 14 C reaction, neutron dose (mainly fast and epithermal neutrons) and gamma-ray dose (external and from capture reaction 1 H(n,γ) 2 D). Because of this the relation between the absorbed dose and the biological effects is very complex and all the above mentioned absorbed dose components should be determined. From this point of view, the recombination chambers can be very useful instruments for characterization of the BNCT beams. They can be used for determination of gamma and high-LET dose components for the characterization of radiation quality of mixed radiation fields by recombination microdosimetric method (RMM). In present work, a graphite high-pressure recombination chamber filled with nitrogen, 10 BF 3 and tissue equivalent gas was used for studies on application of RMM for BNCT dosimetry. The use of these gases or their mixtures opens a possibility to design a recombination chamber for determination of the dose fractions due to gamma radiation, fast neutrons, neutron capture on nitrogen and high LET particles from (n, 10 B) reaction in simulated tissue with different content of 10 B. (author)

SBNCT plan: A 3-dimensional treatment planning system for boron neutron capture therapy

International Nuclear Information System (INIS)

Reinstein, L.E.; Ramsay, E.B.; Gajewski, J.; Ramamoorthy, S.; Meek, A.G.

1993-01-01

The need for accurate and comprehensive 3-dimensional treatment planning for boron neutron capture therapy (BNCT) has been debated for the past several years. Although many argue against the need for elaborate and expensive treatment planning programs which mimic conventional radiotherapy planning systems, it is clear that in order to realize significant gains over conventional fractionated radiation therapy, patients must be treated to the edge of normal tissue tolerance. Just how close to this edge is dictated by the uncertainties in dosimetry. Hence the focus of BNCT planning is the determination of dose distribution throughout normal tissue volumes. Although precise geometric manipulation of the epithermal neutron beam is not achievable, the following variables play an important role in BNCT optimization: patient orientation, dose fractionation, number of fields, megawatt-minutes per fraction, use of surface bolus, and use of collimation. Other variables which are not as easily adjustable and would not, therefore, be part of treatment planning optimization, include external patient contour, internal patient heterogeneities, boron compound distributions, and RBE's. The boron neutron capture therapy planning system developed at SUNY Stony Brook (SBNCT-Plan) was designed as an interactive graphic tool to assist the radiation oncologist in generating the optimum plan for a neutron capture treatment

Application of HVJ envelope system to boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Nakai, Kei; Kurooka, Masaaki; Kaneda, Yasufumi; Yamamoto, Tetsuya; Matsumura, Akira; Asano, Tomoyuki

2006-01-01

Boron Neutron Capture Therapy (BNCT) has been used clinically for the treatment of malignant tumors. Two drugs, p-boronophenylalanine (BPA) and sulfhydral borane (BSH), have been used as boron delivery agents. These drugs seem to be taken up preferentially in solid tumors, but it is uncertain whether therapeutic quantities of boron atoms are taken up by micro-invasive or distant tumor cells. High accumulation and high selective delivery of boron into tumor tissues are the most important requirements to achieve efficient BNCT for malignant tumor. The HVJ envelope (HVJ-E) vector system is a novel fusion-mediated gene delivery system based on inactivated hemagglutinating virus of Japan (HVJ; Sendai virus). Although we developed this vector system for gene transfer, it can also deliver proteins, synthetic oligonucleotides, and drugs. HVJ-liposome, which is liposome fused with HVJ-E, has higher boron trapping efficiency than HVJ-E alone. We report the boron delivery into cultured cells with HVJ-liposome systems. The cellular 10 B concentration after 60 min incubation with HVJ-E containing BSH was 24.9 μg/g cell pellet for BHK-21 cells (baby hamster kidney cells) and 19.4 μg/g cell pellet for SCC VII cells (murine squamous cell carcinoma). These concentrations are higher than that of 60 min incubated cells with BSH containing (100μg 10 B/ml) medium. These results indicate the HVJ-E fused with tumor cell membrane and rapidly delivered boron agents, and that the HVJ-E-mediated delivery system could be applicable to BNCT. Plans are underway to begin neutron radiation experiments in vivo and in vitro. (author)

Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma

Energy Technology Data Exchange (ETDEWEB)

Gabel, D.

1991-06-04

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

Boron Neutron Capture Therapy at European research reactors - Status and perspectives

International Nuclear Information System (INIS)

Moss, R.L.

2004-01-01

Over the last decade. there has been a significant revival in the development of Boron Neutron Capture Therapy (BNCT) as a treatment modality for curing cancerous tumours, especially glioblastoma multiforme and subcutaneous malignant melanoma. In 1987 a European Collaboration on BNCT was formed, with the prime task to identify suitable research reactors in Europe where BNCT could be applied. Due to reasons discussed in this paper, the HFR Petten was chosen as the test-bed for demonstrating BNCT. Currently, the European Collaboration is approaching the start of clinical trials, using epithermal neutrons and borocaptate sodium (BSH) as the 10 B delivery agent. The treatment is planned to start in the first half of 1996. The paper here presents an overview on the principle of BNCT, the requirements imposed on a research reactor in order to be considered for BNCT, and the perspectives for other European materials testing reactors. A brief summary on the current status of the work at Petten is given, including: the design, construction and characterisation of the epithermal neutron beam: performance and results of the healthy tissue tolerance study; the development of a treatment planning programme based on the Monte Carlo code MCNP; the design of an irradiation room; and on the clinical trials themselves. (author)

Boron neutron capture therapy for malignant melanoma: An experimental approach

Energy Technology Data Exchange (ETDEWEB)

Larsson, B.S.; Larsson, B.; Roberto, A. (Uppsala Univ. (Sweden))

1989-07-01

Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H-1,2,4-triazole-3-thiol (B-TZT), boronated 5-carboxy-2-thiouracil (B-CTU), and boronated 5-diethylaminomethyl-2-thiouracil (B-DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B-TZT and B-CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B-DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B-TZT, compared with B-CTU. The results suggest that B-TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.

Quorum Quenching Agents: Resources for Antivirulence Therapy

Directory of Open Access Journals (Sweden)

Kaihao Tang

2014-05-01

Full Text Available The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy.

Iodine neutron capture therapy

Science.gov (United States)

Ahmed, Kazi Fariduddin

A new technique, Iodine Neutron Capture Therapy (INCT) is proposed to treat hyperthyroidism in people. Present thyroid therapies, surgical removal and 131I treatment, result in hypothyroidism and, for 131I, involve protracted treatment times and excessive whole-body radiation doses. The new technique involves using a low energy neutron beam to convert a fraction of the natural iodine stored in the thyroid to radioactive 128I, which has a 24-minute half-life and decays by emitting 2.12-MeV beta particles. The beta particles are absorbed in and damage some thyroid tissue cells and consequently reduce the production and release of thyroid hormones to the blood stream. Treatment times and whole-body radiation doses are thus reduced substantially. This dissertation addresses the first of the several steps needed to obtain medical profession acceptance and regulatory approval to implement this therapy. As with other such programs, initial feasibility is established by performing experiments on suitable small mammals. Laboratory rats were used and their thyroids were exposed to the beta particles coming from small encapsulated amounts of 128I. Masses of 89.0 mg reagent-grade elemental iodine crystals have been activated in the ISU AGN-201 reactor to provide 0.033 mBq of 128I. This activity delivers 0.2 Gy to the thyroid gland of 300-g male rats having fresh thyroid tissue masses of ˜20 mg. Larger iodine masses are used to provide greater doses. The activated iodine is encapsulated to form a thin (0.16 cm 2/mg) patch that is then applied directly to the surgically exposed thyroid of an anesthetized rat. Direct neutron irradiation of a rat's thyroid was not possible due to its small size. Direct in-vivo exposure of the thyroid of the rat to the emitted radiation from 128I is allowed to continue for 2.5 hours (6 half-lives). Pre- and post-exposure blood samples are taken to quantify thyroid hormone levels. The serum T4 concentration is measured by radioimmunoassay at

Development and in vitro testing of liposomal gadolinium-formulations for neutron capture therapy of glioblastoma multiforme

International Nuclear Information System (INIS)

Peters, Tanja

2013-01-01

For the improvement of current neutron capture therapy, several liposomal formulations of neutron capture agent gadolinium were developed and tested in a glioma cell model. Formulations were analyzed regarding physicochemical and biological parameters, such as size, zeta potential, uptake into cancer cells and performance under neutron irradiation. The neutron and photon dose derived from intracellular as well as extracellular Gd was calculated via Monte Carlo simulations and set in correlation with the reduction of cell survival after irradiation. To investigate the suitability of Gd as a radiosensitizer for photon radiation, cells were also irradiated with synchrotron radiation in addition to clinically used photons generated by linear accelerator. Irradiation with neutrons led to significantly lower survival for Gd-liposome-treated F98 and LN229 cells, compared to irradiated control cells and cells treated with non-liposomal Gd-DTPA. Correlation between Gd-content and -dose and respective cell survival displayed proportional relationship for most of the applied formulations. Photon irradiation experiments showed the proof-of-principle for the radiosensitizer approach, although the photon spectra currently used have to be optimized for higher efficiency of the radiosensitizer. In conclusion, the newly developed Gd-liposomes show great potential for the improvement of radiation treatment options for highly malignant glioblastoma.

Neutron capture therapy beams at the MIT Research Reactor

International Nuclear Information System (INIS)

Choi, J.R.; Clement, S.D.; Harling, O.K.; Zamenhof, R.G.

1990-01-01

Several neutron beams that could be used for neutron capture therapy at MITR-II are dosimetrically characterized and their suitability for the treatment of glioblastoma multiforme and other types of tumors are described. The types of neutron beams studied are: (1) those filtered by various thicknesses of cadmium, D2O, 6Li, and bismuth; and (2) epithermal beams achieved by filtration with aluminum, sulfur, cadmium, 6Li, and bismuth. Measured dose vs. depth data are presented in polyethylene phantom with references to what can be expected in brain. The results indicate that both types of neutron beams are useful for neutron capture therapy. The first type of neutron beams have good therapeutic advantage depths (approximately 5 cm) and excellent in-phantom ratios of therapeutic dose to background dose. Such beams would be useful for treating tumors located at relatively shallow depths in the brain. On the other hand, the second type of neutron beams have superior therapeutic advantage depths (greater than 6 cm) and good in-phantom therapeutic advantage ratios. Such beams, when used along with bilateral irradiation schemes, would be able to treat tumors at any depth in the brain. Numerical examples of what could be achieved with these beams, using RBEs, fractionated-dose delivery, unilateral, and bilateral irradiation are presented in the paper. Finally, additional plans for further neutron beam development at MITR-II are discussed

Towards gadolinium neutron capture therapy

International Nuclear Information System (INIS)

Stalpers, L.; Kuipers, S.; Vroegindeweij, C.; Stecher-Rasmussen, F.; Slotman, B.

2000-01-01

As glioblastoma multiforme has macroscopic areas with poor vascularisation, and thereby poor uptake of an NCT-agent, the long-range γ-rays from GdNCT might enhance dose deposition compared to BNCT and to conformal photon therapy. Multicellular spheroids from a human glioblastoma cell line (Gli-6) were irradiated with conventional X-rays, with neutrons only (from the NRG Argonaut Reactor, LFR), and with neutrons (from the LFR) + 157 Gd-DTPA (240 ppm 157 Gd). Preliminary results demonstrate that after neutron irradiation in the presence of 157 Gd, the spheroids showed growth arrest. By 3D treatment planning calculations on MRI's from patients with brain tumours, dose volume histograms (DVH) for GdNCT were compared to DVH for conventional conformal radiotherapy. The calculations indicate that GdNCT on patients with large, deep-seated tumours yields better tumour/brain dose distribution than conformal radiotherapy. (author)

Slow neutron capture therapy for malignant glioma (boron or lithium neutron capture therapy)

International Nuclear Information System (INIS)

Hatanaka, Hiroshi

1981-01-01

In recurrent glioblastoma, the mean survival period is approx. 6 months by the routine methods of treatment, but is extended more than 3-fold by neutron capture therapy. This method and a routine method with 60 Co or an accelerator were used for comparison in the clinical treatment of 26 patients with supratentorial malignant glioma. There were no significant differences as for prognostic factors of the group treated by this method and those of the control group; No. of cases 14 and 12, the mean age 46 and 53.5 yr, and the stage (TNM) 3.14 and 2.83, respectively. As of the end of Feb. 1980, this method showed a lifeprolonging effect 3 times that of the control, the mean survival period being 67 weeks for this method and 21 for the control. Although 100% improvement was observed in about one half of the cases by this method, the control group showed improvement of only 80% at maximum. It is also possible to treat any deep portion of the brain with thermal neutrons. As a Boron compound, mercaptoundecahydrododecarborate with a low toxicity has been put into practical use for brain tumors, and as Li, the use of 6 LiCl for lung cancer is under examination. (Chiba, N.)

Dose modification factors in boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Allen, B.J. (Australian Nuclear Science and Technology Organization (ANSTO), Menai (Australia))

1993-01-01

The effective treatment depth and therapeutic ratio in boron neutron capture therapy (BNCT) depend on a number of macroscopic dose factors such as boron concentrations in the tumor, normal tissue and blood. However, the role of various microscopic dose modification factors can be of critical importance in the evaluation of normal tissue tolerance levels. An understanding of these factors is valuable in designing BNCT experiments and the selection of appropriate boron compounds. These factors are defined in this paper and applied to the case of brain tumors with particular attention to capillary endothelial cells and oligodendrocytes. (orig.).

Novel amino-carboxy-dihydroboranes for neutron capture therapy

International Nuclear Information System (INIS)

Boehmel, T.

1985-01-01

The thesis discusses the following topics: I. Synthesis of boron compounds for the neutron capture therapy which are to meet the following requirements: 1. Low toxicity; 2. High boron content; 3. High enrichment and long retention time in the neoplastic tissue and simultaneous low concentration in blood and normal tissue; 4. Independent cytostatic effects; 5. Functional groups which allow a connection with polymers. II. Presentation of compounds with increased 10 B content. III. Examination of the distribution of boric substances in living organisms by means of a quantitative analysis of the boron content. (orig./PW) [de

Monte Carlo based dosimetry and treatment planning for neutron capture therapy of brain tumors

International Nuclear Information System (INIS)

Zamenhof, R.G.; Clement, S.D.; Harling, O.K.; Brenner, J.F.; Wazer, D.E.; Madoc-Jones, H.; Yanch, J.C.

1990-01-01

Monte Carlo based dosimetry and computer-aided treatment planning for neutron capture therapy have been developed to provide the necessary link between physical dosimetric measurements performed on the MITR-II epithermal-neutron beams and the need of the radiation oncologist to synthesize large amounts of dosimetric data into a clinically meaningful treatment plan for each individual patient. Monte Carlo simulation has been employed to characterize the spatial dose distributions within a skull/brain model irradiated by an epithermal-neutron beam designed for neutron capture therapy applications. The geometry and elemental composition employed for the mathematical skull/brain model and the neutron and photon fluence-to-dose conversion formalism are presented. A treatment planning program, NCTPLAN, developed specifically for neutron capture therapy, is described. Examples are presented illustrating both one and two-dimensional dose distributions obtainable within the brain with an experimental epithermal-neutron beam, together with beam quality and treatment plan efficacy criteria which have been formulated for neutron capture therapy. The incorporation of three-dimensional computed tomographic image data into the treatment planning procedure is illustrated. The experimental epithermal-neutron beam has a maximum usable circular diameter of 20 cm, and with 30 ppm of B-10 in tumor and 3 ppm of B-10 in blood, it produces a beam-axis advantage depth of 7.4 cm, a beam-axis advantage ratio of 1.83, a global advantage ratio of 1.70, and an advantage depth RBE-dose rate to tumor of 20.6 RBE-cGy/min (cJ/kg-min). These characteristics make this beam well suited for clinical applications, enabling an RBE-dose of 2,000 RBE-cGy/min (cJ/kg-min) to be delivered to tumor at brain midline in six fractions with a treatment time of approximately 16 minutes per fraction

Considerations for boron neutron capture therapy studies

International Nuclear Information System (INIS)

Faria Gaspar, P. de.

1994-01-01

Radiotherapy is indispensable as a mean to eradicate deeply or infiltrating tumor tissue that can not be removed surgically. Therefore, it is not selective and may also kill the surrounding health tissue. The principle of BNCT (Boron Neutron Capture Therapy) consist in targeting a tumor selectively with a boron-10 compound. This nuclide has a large capture cross section for thermal neutrons and the nuclear reaction and the delivered energy in locus will selective the tumor. Since its initial proposal in 1963 BNCT has made much progress, however it is not used in a routine treatment. In this work it was approached some complex procedures, as the obtention of selective boron compounds, the adequate set up of neutron beams, the biodistribution, the in vivo and in vitro studies, and also human patients treatments. This work provide fundamentals about BNCT to professional of different areas of knowledge since it comprises multidisciplinary study. It includes appendixes for the ones not related to the field for a better comprehension of the many aspects involved. It is also presented a glossary containing technical and basic aspects involved. It is also presented a glossary containing technical and basic terms referred in the work. (author). 174 refs, 1 fig, 12 apps

Leukemia after therapy with alkylating agents for childhood cancer

International Nuclear Information System (INIS)

Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

1987-01-01

The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

Rates of nickel(II) capture from complexes with NTA, EDDA, and related tetradentate chelating agents by the hexadentate chelating agents EDTA and CDTA: Evidence of a "semijunctive" ligand exchange pathway

Science.gov (United States)

Boland, Nathan E.; Stone, Alan T.

2017-09-01

Many siderophores and metallophores produced by soil organisms, as well as anthropogenic chelating agent soil amendments, rely upon amine and carboxylate Lewis base groups for metal ion binding. UV-visible spectra of metal ion-chelating agent complexes are often similar and, as a consequence, whole-sample absorbance measurements are an unreliable means of monitoring the progress of exchange reactions. In the present work, we employ capillary electrophoresis to physically separate Ni(II)-tetradentate chelating agent complexes (NiL) from Ni(II)-hexadentate chelating agent complexes (NiY) prior to UV detection, such that progress of the reaction NiL + Y → NiY + L can be conveniently monitored. Rates of ligand exchange for Ni(II) are lower than for other +II transition metal ions. Ni(II) speciation in environmental media is often under kinetic rather than equilibrium control. Nitrilotriacetic acid (NTA), with three carboxylate groups all tethered to a central amine Lewis base group, ethylenediamine-N,N‧-diacetic acid (EDDA), with carboxylate-amine-amine-carboxylate groups arranged linearly, plus four structurally related compounds, are used as tetradentate chelating agents. Ethylenediaminetetraacetic acid (EDTA) and the structurally more rigid analog trans-cyclohexaneethylenediaminetetraacetic acid (CDTA) are used as hexadentate chelating agents. Effects of pH and reactant concentration are explored. Ni(II) capture by EDTA was consistently more than an order of magnitude faster than capture by CDTA, and too fast to quantify using our capillary electrophoresis-based technique. Using NiNTA as a reactant, Ni(II) capture by CDTA is independent of CDTA concentration and greatly enhanced by a proton-catalyzed pathway at low pH. Using NiEDDA as reactant, Ni(II) capture by CDTA is first order with respect to CDTA concentration, and the contribution from the proton-catalyzed pathway diminished by CDTA protonation. While the convention is to assign either a disjunctive

Neutron capture therapy of ocular melanoma: dosimetry and microdosimetry approaches

International Nuclear Information System (INIS)

Pignol, J.P.; Methlin, G.; Abbe, J.C.; Lefebvre, O.; Sahel, J.

1994-01-01

Neutron capture therapy (NCT) aims at destroying cancerous cells with the α and 7 Li particles produced by the neutron capture reaction on 10 B. This note reports on the study of the boron distribution in tissues on an animal model (nude mice) xenografted with a human ocular melanoma after an i.p.injection of 2g/kg of 10 B-BPA and in cells cultured in the presence of 530 μmol/l of 10 B-BPA. A concentration of 64 ppm of 10 B in the active part of the tumour with a ratio of concentrations versus the skin of 3.7 are observed. Investigations on cells reveal the presence of boron in the cytoplasm. The biological, dosimetric and microdosimetric consequences of these findings are discussed. (authors). 15 refs., 2 tabs., 2 figs

Novel agents for anti-platelet therapy

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Ji Xuebin

2011-11-01

Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

Evaluation of carboranylporphyrins as boron delivery agents for neutron capture therapy

International Nuclear Information System (INIS)

Kawabata, Shinji; Barth, Rolf F.; Yang, Weilian; Wu, Gong; Binns, Peter J.; Riley, Kent J.; Ongayi, Owendi; Gottumukkala, Vijay; Vicente, Graca H.

2006-01-01

The goals of the present study were two-fold. First, to determine the biodistribution of three carboranyl-porphyrins, designated H 2 DCP, H 2 TCP and H 2 TBP following intracerebral (i.c.) administration by means of convection enhanced delivery (CED) to F98 glioma bearing rats. Tumor boron concentrations immediately after CED were 36 and 88 μg/g for H 2 DCP and H 2 TCP, respectively, and were 103 and 62 μg/g for H 2 TCP and H 2 TBP, respectively, 24h after termination of CED. The corresponding normal brain concentrations were 5.2, 3.3 and 0.8 μg/g, and blood and liver concentrations all were 2 TCP and H 2 TBP as boron delivery agents in F98 glioma bearing rats. BNCT was carried out at the Massachusetts Institute of Technology (MIT) Research Reactor (MITRR) 24 h after CED of 200 μl of either 0.5 mg of H 2 TCP or H 2 TBP. Untreated control rats all died within 29 days after tumor implantation and had a mean survival time (MST) of 23±3 days and irradiated controls had a MST of 27±3 days. Animals that received H 2 TCP by CED, followed by BNCT, had a MST of 35±4 days and animals received H 2 TBP had a MST of 44±10 days. Further studies were carried out using H 2 TBP at a dose of 0.2 mg administered by a Harvard pump, either alone or in combination with i.v. BPA, and the corresponding MSTs were 34±3 d and 43±9 d, respectively. Histopathologic examination of the brains of animals that died revealed large numbers of porphyrin laden macrophages and extracellular accumulations of free porphyrin indicating that tumor cell uptake was suboptimal. Further studies are planned to synthesize and evaluate new compounds that will have enhanced cellular uptake and efficacy as boron delivery agents for NCT. (author)

Physico-technical progress in neutron-capture therapy method

International Nuclear Information System (INIS)

Kanda, Keiji; Furubayashi, Toru; Aoki, Kazuhiko

1985-01-01

This paper describes mainly development studies on the determination method of in vivo 10 B for the purpose of employment for neutron capture therapy for malignant melanoma and other tumors. To darify the efficacy of the neutron capture therapy, it is necessary to determine 10 B concentration in the diseased part. This study aimed at in vivo 10 B concention determination in living sample to the level of ppm order with 10 % of analytical error within 1 hour, and these determination conditions were satified by prompt γ-ray (478 keV) determination of 10 B (n, αγ) 7 Li reaction. This method required no sample pretreatment. Further, data normalization by γ-ray of H(n, γ)D reaction permitted no disturbance by sample shape or size. Lower limit of detection of the proposed method was estimated in terms of measuring time and statistical error by the equations of 10 B concentration and error analysis derived by the authors. As for the effect of prompt γ-rays of 23 Na(n, γ) 24 Na and 6 Li(n, γ) 7 Li reactions, it was clarified that the former showed no disturbance but some correction was necessary in case of less than 0.1 g of smaple size owing to the latter reaction. In vivo sample determination showed the proposed method was practical. In this paper some results of phantom experiment for in vivo non-destructive 10 B measurement and related simulation calculation, and examination of effect of (γ, n) reaction in heavy water of biomedical irradiation equipment on radiation quality were also described. (Takagi, S.)

Experience of boron neutron capture therapy in Japan

International Nuclear Information System (INIS)

Kanda, K.

2004-01-01

Four research reactors are currently licensed for medical application in Japan. As of July 1995, approximately 210 clinical irradiations using these research reactors have been done for brain and skin tumors as shown. The number of chief medical doctors certified by the Government is eleven so far. Among them, eight doctors have already treated tumor patients using the Kyoto University Reactor (KUR, 5MW). Recently in USA clinical trials have been restarted using epithermal neutrons at MIT and BNL. In this paper, the experience of clinical trials of boron neutron capture therapy (BNCT) which have been performed in Japan, mainly physics studies, are reviewed, and current studies are also introduced

Antitumor potential induction and free radicals production in melanoma cells by Boron Neutron Capture Therapy

Energy Technology Data Exchange (ETDEWEB)

Faiao-Flores, F. [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)] [Faculty of Medicine, University of Sao Paulo, 455 Doutor Arnaldo Avenue, Sao Paulo (Brazil); Coelho, P.R.P.; Muniz, R.O.R.; Souza, G.S. [Institute for Nuclear and Energy Research, 2242 Lineu Prestes Avenue, Sao Paulo (Brazil); Arruda-Neto, J. [Physics Institute, University of Sao Paulo, 187 Matao Street, Sao Paulo (Brazil)] [FESP, Sao Paulo Engineering School, 5520 Nove de Julho Avenue, Sao Paulo (Brazil); Maria, Durvanei A., E-mail: durvaneiaugusto@yahoo.com.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

2011-12-15

Antiproliferative and oxidative damage effects occurring in Boron Neutron Capture Therapy (BNCT) in normal fibroblasts and melanoma cell lines were analyzed. Melanoma cells and normal fibroblasts were treated with different concentrations of Boronophenylalanine and irradiated with thermal neutron flux. The cellular viability and the oxidative stress were determined. BNCT induced free radicals production and proliferative potential inhibition in melanoma cells. Therefore, this therapeutic technique could be considered efficient to inhibit growth of melanoma with minimal effects on normal tissues. - Highlights: Black-Right-Pointing-Pointer Boron Neutron Capture Therapy (BNCT) induces melanoma cell death. Black-Right-Pointing-Pointer BNCT stimulates free radicals production and proliferative inhibition in melanoma cells. Black-Right-Pointing-Pointer It produces tumor membrane degeneration and destruction with apoptotic bodies formation. Black-Right-Pointing-Pointer This therapy damages tumor cells selectively, with minimum effects on normal adjacent tissue.

Boron neutron capture therapy: Brain Tumor Treatment Evaluation Program

International Nuclear Information System (INIS)

Griebenow, M.L.; Dorn, R.V. III; Gavin, P.R.; Spickard, J.H.

1988-01-01

The United States (US) Department of Energy (DOE) recently initiated a focused, multidisciplined program to evaluate Boron Neutron Capture Therapy (BNCT) for the treatment of brain tumors. The program, centered at the DOE/endash/Idaho National Engineering Laboratory (INEL), will develop the analytical, diagnostic and treatment tools, and the database required for BNCT technical assessment. The integrated technology will be evaluated in a spontaneously-occurring canine brain-tumor model. Successful animal studies are expected to lead to human clinical trials within four to five years. 2 refs., 3 figs

Research needs for neutron capture therapy

International Nuclear Information System (INIS)

1995-01-01

Key issues and questions addressed by the workshop related to optimization of Boron Neutron Capture Therapy (BNCT), in general, and to the possibility of success of the present BNCT trials at Brookhaven National Laboratory (BNL) and Massachusetts Institute of Technology (MIT), in particular. Both trials use nuclear fission reactors as neutron sources for BNCT of glioblastoma multiforme (BNL) and of deep seated melanoma (MIT). Presentations and discussions focussed on optimal boron-labeled compounds, mainly for brain tumors such as glioblastoma multiforme, and the best mode of compound delivery to the tumor. Also, optimizing neutron irradiation with dose delivery to the tumor cells and the issues of dosimetry of BNCT especially in the brain were discussed. Planning of treatment and of follow-up of patients, coordination of BNCT at various treatment sites, and the potential of delivering BNCT to various types of cancer with an appropriately tailored protocol were additional issues. The need for multicentric interdisciplinary cooperation among the different medical specialties was highlighted

Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy.

Science.gov (United States)

Mi, Peng; Dewi, Novriana; Yanagie, Hironobu; Kokuryo, Daisuke; Suzuki, Minoru; Sakurai, Yoshinori; Li, Yanmin; Aoki, Ichio; Ono, Koji; Takahashi, Hiroyuki; Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2015-06-23

Gadolinium (Gd) chelates-loaded nanocarriers have high potential for achieving magnetic resonance imaging (MRI)-guided Gd neutron capture therapy (GdNCT) of tumors. Herein, we developed calcium phosphate micelles hybridized with PEG-polyanion block copolymers, and incorporated with the clinical MRI contrast agent Gd-diethylenetriaminepentaacetic acid (Gd-DTPA/CaP). The Gd-DTPA/CaP were nontoxic to cancer cells at the concentration of 100 μM based on Gd-DTPA, while over 50% of the cancer cells were killed by thermal neutron irradiation at this concentration. Moreover, the Gd-DTPA/CaP showed a dramatically increased accumulation of Gd-DTPA in tumors, leading to the selective contrast enhancement of tumor tissues for precise tumor location by MRI. The enhanced tumor-to-blood distribution ratio of Gd-DTPA/CaP resulted in the effective suppression of tumor growth without loss of body weight, indicating the potential of Gd-DTPA/CaP for safe cancer treatment.

Use of the Power Burst Facility for boron neutron capture therapy

International Nuclear Information System (INIS)

Crocker, J.G.; Griebenow, M.L.; Leatham, J.

1990-01-01

A program is under development at the Idaho National Engineering Laboratory (INEL) that involves using the Power Burst Facility (PBF) for research into boron neutron capture therapy (BNCT). BNCT utilizes the ionizing energy from boron-neutron capture to stop reproduction of or destroy cells in cancerous tissue in a two-step process. The first step is to selectively concentrate a boron isotope within the tumor cell, that when activated by neutron capture emits highly ionizing, short range particles. The second step involves activation of the isotope only in the vicinity of the tumor with a narrow neutron beam. The ( 10 B[n, 4 He] 7 Li) reaction with thermal neutrons produces fission products with track lengths approximately equal to a cell diameter. The INEL program includes the modification of the PBF by the addition of a filter and treatment area. The filter will down-scatter high energy neutrons into the epithermal range and remove thermal neutrons and excessively damaging gamma components. The intense source of epithermal neutrons from PBF is considered necessary to achieve optimum therapy for deep-seated tumors with minimum damage to surface tissue. THe neutron filter conceptualized for PBF utilizes aluminum and heavy water to down-scatter neutrons into the proper energy range. Bismuth will be used for gamma shielding and cadmium will remove the thermal neutron contaminant from the beam. The INEL program leads to human clinical trials at PBF which are intended to prove that brain tumors can be successfully treated through noninvasive techniques. Further research into BNCT at PBF for other cancer types is also anticipated

Distribution of exogenous porphyrins in vivo; implications for neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.; Gabel, D.; Hillman, M.; Watts, K.

1982-01-01

Endogenous porphyrins (HpD) are already in clinical use for phototherapy, in which red light is used to stimulate a cytotoxic response in tumors. The evident success, at least with superficial cancers, gives biological evidence of selective concentrations of porphyrins in tumors adequate for therapy. The authors have investigated, in addition, the biodistribution of a synthetic porphyrin (tetraphenylporphinesulfonate, or TPPS) in seven different animal tumor models. Their data, as well as those of others, indicate abundant accumulations of TPPS in tumor. If boronated analogs behave in the same way, boron concentrations would be up to 10 times that needed for therapy. Utilization of such porphyrin analogs in the neutron capture therapy (NCT) procedure is similar in concept to phototherapy currently being used clinically, with the distinct advantage of deeper tissue penetration produced by the activating neutrons

Possible alternation of the blood-brain barrier by boron-neutron capture therapy

International Nuclear Information System (INIS)

Hatanaka, H.; Moritani, M.; Camillo, M.

1991-01-01

In the course of re-assessment of boron-neutron capture therapy (BNCT) for malignant brain tumors, fractionation of neutron irradiation has been proposed. The authors have used BNCT with a single fraction technique during the past 21 years and now decided to study some effects of fractionation. Twenty-two healthy mouse brains were irradiated with thermal neutrons after boron-10 injection (mercaptoundecahydrododecaborate). A second dose of boron-10 was administered and its uptake in the boron-neutron-capture-irradiated brains was determined. A tendency towards increased boron uptake in the moderately BNCT-treated brains was noticed, which may result in increased brain damage if fractionated neutron irradiation is used. (orig.)

Beta-blocking agents during electroconvulsive therapy: a review.

Science.gov (United States)

Boere, E; Birkenhäger, T K; Groenland, T H N; van den Broek, W W

2014-07-01

Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A colorimetric determination of boron in biological sample for boron neutron capture therapy

International Nuclear Information System (INIS)

Camilo, M.A.P.; Tomac Junior, U.

1989-01-01

The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of gliomas and glioblastomas grade III and IV than other therapies. During the treatment of levels of Na 2 10 B 12 H 11 S H must be known in several compartments of the organism and with this purpose the method of colorimetric determination of boron using curcumin was established. This method is simples, reproducible and has adequate sensitivity for this control. (author). 7 refs, 3 figs, 1 tab

Physics of epi-thermal boron neutron capture therapy (epi-thermal BNCT).

Science.gov (United States)

Seki, Ryoichi; Wakisaka, Yushi; Morimoto, Nami; Takashina, Masaaki; Koizumi, Masahiko; Toki, Hiroshi; Fukuda, Mitsuhiro

2017-12-01

The physics of epi-thermal neutrons in the human body is discussed in the effort to clarify the nature of the unique radiologic properties of boron neutron capture therapy (BNCT). This discussion leads to the computational method of Monte Carlo simulation in BNCT. The method is discussed through two examples based on model phantoms. The physics is kept at an introductory level in the discussion in this tutorial review.

Nanotechnology-driven cancer therapy

International Nuclear Information System (INIS)

Hosmane, Narayan S.

2012-01-01

In recent years, much efforts have been devoted to developing nanomaterials-based boron drugs for neutron capture therapy (NCT) and to date, a majority of the studies have proved reasonably promising. Conversely, further in vivo studies and clinical trails are needed to establish them as appropriate boron carriers; this is especially so with the relatively novel boron nanotubes and magnetic nanoparticles. More advanced forms of boron nanotubes can be anticipated as much interest in their synthesis as their future applications. Thus, boron neutron capture therapy (BNCT) is a promising treatment for malignant brain tumors as well as for other types of cancers, such as, liver, prostate, bladder, breasts, head and neck tumors. Current research focuses on both the design and synthesis of high boron containing compounds as BNCT agents, and the search for suitable delivery vehicles. To be suitable BNCT agents, the problem of their low water-solubility needs to be resolved by chemical modification. In the case of magnetic nanoparticles, strategies are required to counter their tendency of embolization and their unclear cytotoxicity must be resolved

Local control of murine melanoma xenografts in nude mice by neutron capture therapy

International Nuclear Information System (INIS)

Allen, B.J.; Corderoy-Buck, S.; Moore, D.E.; Mishima, Y.; Ichihashi, M.

1992-01-01

In recent years considerable progress has been made in the development and implementation of neutron capture therapy (NCT) for the treatment of cancer. In particular, the boron analogue of the melanin precursor phenylalanine, i.e., DL-p-boronophenylalanine (BPA), has been used to demonstrate the regression and cure of Harding-Passey (HP) melanoma in syngeneic mice. However, 18 to 25% cures were obtained for neutron irradiations without boron, suggesting that the neutron dose alone plays an important role. Neutron capture therapy of B-16 melanoma xenografts in nude mice showed substantial tumor regression over 35 days, but the survival rate of NCT treated mice after 7 weeks was only 40-60%. In this paper the authors demonstrate the equivalence of the nude mouse model with a syngeneic model, using the same Harding-Passey murine melanoma line, and delineate the conditions required for maximum differential response between neutron irradiation with and without BPA administration, with complete local control as the end point

A colorimetric determination of boron in biological sample for boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Camillo, M.A.P.; Tomac Junior, U.

1990-01-01

The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of glyemas and gluoblastomas grade III and IV than other therapies. During the treatment the levels of Na 2 10 B 12 H 11 SH must be known in several compartiments of the organism and with this purpose the method of colorimetric determination of boron using curcumine was established. This method is simple, reprodutible and adequate sensitivity for this control. (author) [pt

Boron compounds in neutron capture therapy of tumors

International Nuclear Information System (INIS)

Strouf, O.; Gregor, V.

1986-01-01

In the selective incorporation of a sufficient amount of a compound containing boron isotope 10 B in the tumor tissue for neutron capture therapy, high efficiency is achieved in tumor destruction while sparing the surrounding tissues. In the treatment of brain tumors, 4-carboxy phenylboric acid and the disodium salt of mercaptoundecahydrododecaborate were successfully tested. The use of the compounds minimizes radiation damage to the blood stream of the brain. In case of melanomas the L-DOPA-borate complex, boronophenylalanine and chlorpromazine preparations containing 10 B are used. In the treatment of cancer of the reproductive organs, boron derivatives of estradiol and testosterone have been proven. The immunobiological procedure, i.e., the use of antibodies with bound boron compounds, is being intensively studied. (M.D.)

Proton Neutron Gamma-X Detection (PNGXD): An introduction to contrast agent detection during proton therapy via prompt gamma neutron activation

Science.gov (United States)

Gräfe, James L.

2017-09-01

Proton therapy is an alternative external beam cancer treatment modality to the conventional linear accelerator-based X-ray radiotherapy. An inherent by-product of proton-nuclear interactions is the production of secondary neutrons. These neutrons have long been thought of as a secondary contaminant, nuisance, and source of secondary cancer risk. In this paper, a method is proposed to use these neutrons to identify and localize the presence of the tumor through neutron capture reactions with the gadolinium-based MRI contrast agent. This could provide better confidence in tumor targeting by acting as an additional quality assurance tool of tumor position during treatment. This effectively results in a neutron induced nuclear medicine scan. Gadolinium (Gd), is an ideal candidate for this novel nuclear contrast imaging procedure due to its unique nuclear properties and its widespread use as a contrast agent in MRI. Gd has one of the largest thermal neutron capture cross sections of all the stable nuclides, and the gadolinium-based contrast agents localize in leaky tissues and tumors. Initial characteristics of this novel concept were explored using the Monte Carlo code MCNP6. The number of neutron capture reactions per Gy of proton dose was found to be approximately 50,000 neutron captures/Gy, for a 8 cm3 tumor containing 300 ppm Gd at 8 cm depth with a simple simulation designed to represent the active delivery method. Using the passive method it is estimated that this number can be up to an order of magnitude higher. The thermal neutron distribution was found to not be localized within the spread out Bragg peak (SOBP) for this geometrical configuration and therefore would not allow for the identification of a geometric miss of the tumor by the proton SOBP. However, this potential method combined with nuclear medicine imaging and fused with online CBCT and prior MRI or CT imaging could help to identify tumor position during treatment. More computational and

Analytical dosimetry for spontaneous tumor dogs receiving boron neutron capture therapy

International Nuclear Information System (INIS)

Wheeler, F.J.; Atkinson, C.A.; Gavin, P.R.

1992-01-01

The dog irradiation project of the Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program is administered by Washington State University (WSU) with analytical and physical dosimetry provided by the Idaho National Engineering Laboratory (INEL). One subtask of this project includes BNCT safety studies for dogs with spontaneously-occurring brain tumors. The boron compound (Na 2 B 12 H 11 SH or BSH) was administered and single irradiations performed using the epithermal-neutron beam at the Brookhaven Medical Research Reactor (BMRR). The main goal of the study was not to provide therapy, but to determine tumorcidal effect while administering a subtolerance dose to healthy tissue. Irradiation times were based on delivery of 19 Gy peak physical dose to the blood

Proceedings of workshop on 'boron science and boron neutron capture therapy'

Energy Technology Data Exchange (ETDEWEB)

Kitaoka, Y. [ed.

1998-12-01

This volume contains the abstracts and programs of the 8th (1996), 9th (1997) and 10th (1998) of the workshop on 'the Boron Science and Boron Neutron Capture Therapy' and the recent progress reports especially subscribed. The 11 of the presented papers are indexed individually. (J.P.N.)

Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

Energy Technology Data Exchange (ETDEWEB)

Joel, D.D.; Coderre, J.A.; Chanana, A.D. [Brookhaven National Lab., Upton, NY (United States). Medical Dept.

1996-12-31

Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope {sup 10}B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/{sup 10}B reactions ({sup 10}B(n,{alpha}){sup 7}Li) resulting in the production of localized high LET radiation from alpha and {sup 7}Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams.

Boron neutron capture therapy of malignant brain tumors at the Brookhaven Medical Research Reactor

International Nuclear Information System (INIS)

Joel, D.D.; Coderre, J.A.; Chanana, A.D.

1996-01-01

Boron neutron capture therapy (BNCT) is a bimodal form of radiation therapy for cancer. The first component of this treatment is the preferential localization of the stable isotope 10 B in tumor cells by targeting with boronated compounds. The tumor and surrounding tissue is then irradiated with a neutron beam resulting in thermal neutron/ 10 B reactions ( 10 B(n,α) 7 Li) resulting in the production of localized high LET radiation from alpha and 7 Li particles. These products of the neutron capture reaction are very damaging to cells, but of short range so that the majority of the ionizing energy released is microscopically confined to the vicinity of the boron-containing compound. In principal it should be possible with BNCT to selectively destroy small nests or even single cancer cells located within normal tissue. It follows that the major improvements in this form of radiation therapy are going to come largely from the development of boron compounds with greater tumor selectivity, although there will certainly be advances made in neutron beam quality as well as the possible development of alternative sources of neutron beams, particularly accelerator-based epithermal neutron beams

Long-survivors of glioblatoma treated with boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Kageji, T.; Mizobuchi, Y.; Nagahiro, S.; Nakagawa, Y.; Kumada, H.

2011-01-01

The purpose of this study was to compare the radiation dose between long-survivors and non-long-survivors in patients with glioblatoma (GBM) treated with boron neutron capture therapy (BNCT). Among 23 GBM patients treated with BNCT, there were five patients who survived more than three years after diagnosis. The physical and weighted dose of the minimum gross tumor volume (GTV) of long-survivors was much higher than that of non-long survivors with significant statistical differences.

Universal algorithm for diagnosis of biventricular capture in patients with cardiac resynchronization therapy.

Science.gov (United States)

Jastrzebski, Marek; Kukla, Piotr; Fijorek, Kamil; Czarnecka, Danuta

2014-08-01

An accurate and universal method for diagnosis of biventricular (BiV) capture using a standard 12-lead electrocardiogram (ECG) would be useful for assessment of cardiac resynchronization therapy (CRT) patients. Our objective was to develop and validate such an ECG method for BiV capture diagnosis that would be independent of pacing lead positions-a major confounder that significantly influences the morphologies of paced QRS complexes. On the basis of an evaluation of 789 ECGs of 443 patients with heart failure and various right ventricular (RV) and left ventricular (LV) lead positions, the following algorithm was constructed and validated. BiV capture was diagnosed if the QRS in lead I was predominantly negative and either V1 QRS was predominantly positive or V6 QRS was of negative onset and predominantly negative (step 1), or if QRS complex duration was capture. The algorithm showed good accuracy (93%), sensitivity (97%), and specificity (90%) for detection of loss of LV capture. The performance of the algorithm did not differ among apical, midseptal, and outflow tract RV lead positions and various LV lead positions. LV capture leaves diagnostic hallmarks in the fused BiV QRS related to different vectors of depolarization and more rapid depolarization of the ventricles. An accurate two-step ECG algorithm for BiV capture diagnosis was developed and validated. This algorithm is universally applicable to all CRT patients, regardless of the positions of the pacing leads. ©2014 Wiley Periodicals, Inc.

Monte Carlo calculations on efficiency of boron neutron capture therapy for brain cancer

International Nuclear Information System (INIS)

Awadalla, Galaleldin Mohamed Suliman

2015-11-01

The search for ways to treat cancer has led to many different treatments, including surgery, chemotherapy, and radiation therapy. Among these treatments, boron neutron capture therapy (BNCT) has shown promising results. BNCT is a radiotherapy treatment modality that has been proposed to treat brain cancer. In this technique, cancerous cells are being injected with 1 0B and irradiated by thermal neutrons to increase the probability of 1 0B (n, a)7 L i reaction to occur. This reaction can potentially deliver a high radiation dose sufficient to kill cancer cells by concentrating boron in them. The short rang of 1 0B (n, a) 7 L i reaction limits the damage to only cancerous cells without affecting healthy tissues. The effectiveness and safety of radiotherapy are dependent on the radiation dose delivered to the tumor and healthy tissues. In this thesis, after reviewing the basics and working principles of boron neutron capture therapy (BNCT), monte Carlo simulations were carried out to model a thermal neutron source suitable for BNCT and to examine the performance of proposed model when used to irradiate a sample of boron containing both 1 0B and 1 1B isotopes. MCNP5 code was used to examine the modeled neutron source through different shielding materials. The results were presented, analyzed and discussed at the end of the work. (author)

Commercial Clinical Application of Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

1999-01-01

CRADA No. 95-CR-09 among the LITCO--now Bechtel BWXT Idaho, LLC; a private company, Neutron Therapies Limited Liability Company, NTL formerly Ionix Corporation; and Washington State University was established in 1996 to further the development of BNCT. NTL has established a laboratory for the synthesis, under US FDA approved current Good Manufacturing Practices (cGMP) guidelines, of key boron intermediates and final boron agents for BNCT. The company has focused initially on the development of the compound GB-10 (Na 2 B 10 H 10 ) as the first boron agent of interest. An Investigational New Drug (IND) application for GB-10 has been filed and approved by the FDA for a Phase I human biodistribution trial in patients with non-small cell lung cancer and glioblastoma multiforme at UW under the direction of Professor Keith Stelzer, Principal Investigator (PI). These trials are funded by NTL under a contract with the UW, Department of Radiation Oncology, and the initial phases are nearing completion. Initial results show that boron-10 concentrations on the order of 100 micrograms per gram (100 ppm) can be achieved and maintained in blood with no indication of toxicity

Plastic scintillation dosimetry for radiation therapy: minimizing capture of Cerenkov radiation noise

International Nuclear Information System (INIS)

Beddar, A Sam; Suchowerska, Natalka; Law, Susan H

2004-01-01

Over the last decade, there has been an increased interest in scintillation dosimetry using small water-equivalent plastic scintillators, because of their favourable characteristics when compared with other more commonly used detector systems. Although plastic scintillators have been shown to have many desirable dosimetric properties, as yet there is no successful commercial detector system of this type available for routine clinical use in radiation oncology. The main factor preventing this new technology from realizing its full potential in commercial applications is the maximization of signal coupling efficiency and the minimization of noise capture. A principal constituent of noise is Cerenkov radiation. This study reports the calculated capture of Cerenkov radiation by an optical fibre in the special case where the radiation is generated by a relativistic particle on the fibre axis and the fibre axis is parallel to the Cerenkov cone. The fraction of radiation captured is calculated as a function of the fibre core refractive index and the refractive index difference between the core and the cladding of the fibre for relativistic particles. This is then used to deduce the relative intensity captured for a range of fibre core refractive indices and fibre core-cladding refractive index differences. It is shown that the core refractive index has little effect on the amount of radiation captured compared to the refractive index difference. The implications of this result for the design of radiation therapy plastic scintillation dosimeters are considered

The Boron Neutron Capture Therapy (BNCT) Project at the TRIGA Reactor in Mainz, Germany

DEFF Research Database (Denmark)

Hampel, G.; Grunewald, C.; Schütz, C.

2011-01-01

The thermal column of the TRIGA reactor in Mainz is being used very effectively for medical and biological applications. The BNCT (boron neutron capture therapy) project at the University of Mainz is focussed on the treatment of liver tumours, similar to the work performed at Pavia (Italy) a few ...

Capturing multi-stage fuzzy uncertainties in hybrid system dynamics and agent-based models for enhancing policy implementation in health systems research.

Science.gov (United States)

Liu, Shiyong; Triantis, Konstantinos P; Zhao, Li; Wang, Youfa

2018-01-01

In practical research, it was found that most people made health-related decisions not based on numerical data but on perceptions. Examples include the perceptions and their corresponding linguistic values of health risks such as, smoking, syringe sharing, eating energy-dense food, drinking sugar-sweetened beverages etc. For the sake of understanding the mechanisms that affect the implementations of health-related interventions, we employ fuzzy variables to quantify linguistic variable in healthcare modeling where we employ an integrated system dynamics and agent-based model. In a nonlinear causal-driven simulation environment driven by feedback loops, we mathematically demonstrate how interventions at an aggregate level affect the dynamics of linguistic variables that are captured by fuzzy agents and how interactions among fuzzy agents, at the same time, affect the formation of different clusters(groups) that are targeted by specific interventions. In this paper, we provide an innovative framework to capture multi-stage fuzzy uncertainties manifested among interacting heterogeneous agents (individuals) and intervention decisions that affect homogeneous agents (groups of individuals) in a hybrid model that combines an agent-based simulation model (ABM) and a system dynamics models (SDM). Having built the platform to incorporate high-dimension data in a hybrid ABM/SDM model, this paper demonstrates how one can obtain the state variable behaviors in the SDM and the corresponding values of linguistic variables in the ABM. This research provides a way to incorporate high-dimension data in a hybrid ABM/SDM model. This research not only enriches the application of fuzzy set theory by capturing the dynamics of variables associated with interacting fuzzy agents that lead to aggregate behaviors but also informs implementation research by enabling the incorporation of linguistic variables at both individual and institutional levels, which makes unstructured linguistic data

The Swedish facility for boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Skoeld, K.; Capala, J. [Studsvik Medical AB (Sweden); Kierkegaard, J.; Haakansson, R. [Studsvik Nuclear AB (Sweden); Gudowska, I. [Karolinska Institute (Sweden)

2000-10-01

A BNCT (Boron Neutron Capture Therapy) facility has been constructed at the R2-0 reactor at Studsvik, Sweden. R2-0 is a 1 MW, open core, pool reactor. The reactor core is suspended on a movable tower and can be positioned anywhere in the pool. The BNCT facility includes two adjacent, parallel filter/moderator configurations and the reactor core is positioned in front of any of them as appropriate. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range and with an extended collimator for convenient patient positioning. The other beam has been designed for radiobiological research and is equipped with a heavy water moderator and a large irradiation cavity with a uniform field of thermal neutrons. (author)

The Swedish facility for boron neutron capture therapy

International Nuclear Information System (INIS)

Skoeld, K.; Capala, J.; Kierkegaard, J.; Haakansson, R.; Gudowska, I.

2000-01-01

A BNCT (Boron Neutron Capture Therapy) facility has been constructed at the R2-0 reactor at Studsvik, Sweden. R2-0 is a 1 MW, open core, pool reactor. The reactor core is suspended on a movable tower and can be positioned anywhere in the pool. The BNCT facility includes two adjacent, parallel filter/moderator configurations and the reactor core is positioned in front of any of them as appropriate. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range and with an extended collimator for convenient patient positioning. The other beam has been designed for radiobiological research and is equipped with a heavy water moderator and a large irradiation cavity with a uniform field of thermal neutrons. (author)

Development of inverse-planning system for neutron capture therapy

International Nuclear Information System (INIS)

Kumada, Hiroaki; Yamamoto, Kazuyoshi; Maruo, Takeshi

2006-01-01

To lead proper irradiation condition effectively, Japan Atomic Energy Agency (JAEA) is developing an inverse-planning system for neutron capture therapy (NCT-IPS) based on the JAEA computational dosimetry system (JCDS) for BNCT. The leading methodology of an optimum condition in the NCT-IPS has been applied spatial channel theory with adjoint flux solution of Botzman transport. By analyzing the results obtained from the adjoint flux calculations according to the theory, optimum incident point of the beam against the patient can be found, and neutron spectrum of the beam which can generate ideal distribution of neutron flux around tumor region can be determined. The conceptual design of the NCT-IPS was investigated, and prototype of NCT-IPS with JCDS is being developed. (author)

Some thoughts on tolerance, dose, and fractionation in boron neutron capture therapy

International Nuclear Information System (INIS)

Gahbauer, R.; Goodman, J.; Blue, T.

1988-01-01

Unique to boron neutron capture therapy, the tolerance very strongly depends on the boron concentration in normal brain, skin and blood. If one first considers the ideal situation of a 2 KeV beam and a compound clearing from normal tissues and blood, the tolerance dose to epithermal beams relates to the maximum tolerated capture gamma dose and capture high LET dose, H (n,gamma)D and N(n,p) 14 C. The authors can relate this gamma and high LET dose to known clinical experience. Assuming gamma and high LET dose ratios as given by Fairchild and Bond, one may first choose a clearly safe high LET whole brain dose and calculate the unavoidably resulting gamma dose. To a first approximation 500 cGy of high LET dose results in 3,000 cGy gamma dose. One can speculate that this approximates the tolerance of whole brain to the 2 KeV beam with no contributing boron dose if the radiation is fractionated. It would clearly be beyond tolerance in a single fraction where most therapists would be uncomfortable to deliver even one third of the above doses

Response of the oral mucosa to porphyrin mediated boron neutron capture therapy

International Nuclear Information System (INIS)

Morris, G.M.

2003-01-01

Pre-clinical studies are now in progress to develop boron neutron capture therapy (BNCT) modalities for the treatment of head and neck carcinomas. BNCT is a bimodal therapy which involves the administration of a boron-10 enriched compound, that accumulates preferentially in tumours, prior to irradiation with low energy neutrons. These neutrons are captured by boron-10 atoms to produce a highly localised radiation exposure. More recently, it has been demonstrated that various boronated porphyrins can target a variety of tumours. Of the porphyrins evaluated to date, copper tetracarboranylphenyl porphyrin (CuTCPH) is a strong candidate for potential clinical evaluation. It has extremely high specificity for a variety of tumour models. Therapeutic efficacy of CuTCPH mediated BNCT has been demonstrated in pre-clinical studies using the murine EMT-6 carcinoma model. In the present investigation the response of the oral mucosa to CuTCPH mediated boron neutron capture (BNC) irradiation was assessed using a standard rat model (ventral tongue). Single exposure irradiation was carried out on the thermal neutron beam at the Brookhaven Medical Research Reactor, at 3 days after the final injection of the boronated porphyrin. The impact of CuTCPH mediated BNC irradiation on oral mucosa at therapeutically effective exposure times, assessed using the ventral tongue model, was minimal. This was primarily due to the fact that blood boron levels (from CuTCPH) were very low at the time of irradiation. Analysis of the dose-effect data for CuTCPH gave a compound biological effectiveness (CBE) factor of 2.5. It can be concluded that, although, the CBE factor (calculated using blood boron concentrations) was relatively high, CuTCPH mediated BNC irradiation should not cause significant damage at clinically relevant radiation doses. This is because blood boron levels would be very low at the time of irradiation

Initiation of a phase-I trial of neutron capture therapy at the MIT research reactor

International Nuclear Information System (INIS)

Harling, O.K.; Bernard, J.A.; Yam, Chun-Shan

1995-01-01

The Massachusetts Institute of Technology (MIT), the New England Medical Center (NEMC), and Boston University Medical Center (BUMC) initiated a phase-1 trial of boron neutron capture therapy (BNCT) on September 6, 1994, at the 5-MW(thermal) MIT research reactor (MITR). A novel form of experimental cancer therapy, BNCT is being developed for certain types of highly malignant brain tumors such as glioblastoma and melanoma. The results of the phase-1 trials on patients with tumors in the legs or feet are described

Perspectives of boron-neutron capture therapy of malignant brain tumors

Science.gov (United States)

Kanygin, V. V.; Kichigin, A. I.; Krivoshapkin, A. L.; Taskaev, S. Yu.

2017-09-01

Boron neutron capture therapy (BNCT) is characterized by a selective effect directly on the cells of malignant tumors. The carried out research showed the perspective of the given kind of therapy concerning malignant tumors of the brain. However, the introduction of BNCT into clinical practice is hampered by the lack of a single protocol for the treatment of patients and the difficulty in using nuclear reactors to produce a neutron beam. This problem can be solved by using a compact accelerator as a source of neutrons, with the possibility of installation in a medical institution. Such a neutron accelerator for BNCT was developed at Budker Institute of Nuclear Physics, Novosibirsk. A neutron beam was obtained on this accelerator, which fully complies with the requirements of BNCT, as confirmed by studies on cell cultures and experiments with laboratory animals. The conducted experiments showed the relative safety of the method with the absence of negative effects on cell cultures and living organisms, and also confirmed the effectiveness of BNCT for malignant brain tumors.

Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

International Nuclear Information System (INIS)

Mishima, Yutaka

1995-03-01

This issue is the collection of the papers presented thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma. Separate abstracts were prepared for 2 of the papers in this report. The remaining 32 papers were considered outside the subject scope of INIS. (J.P.N.)

Boron neutron capture therapy (BNCT) using fast neutrons: Effects in two human tumor cell lines

International Nuclear Information System (INIS)

Sauerwein, W.; Ziegler, W.; Szypniewski, H.; Streffer, C.

1990-01-01

The results demonstrate that the effect of fast neutrons on cell survival in cell culture can be enhanced by boron neutron capture reaction. Even with lower enhancement ratios, the concept of NCT assisted fast neutron therapy may successfully be applied for tumor treatment with the Essen cyclotron. (orig.)

Dendrimer-based Macromolecular MRI Contrast Agents: Characteristics and Application

Directory of Open Access Journals (Sweden)

Hisataka Kobayashi

2003-01-01

Full Text Available Numerous macromolecular MRI contrast agents prepared employing relatively simple chemistry may be readily available that can provide sufficient enhancement for multiple applications. These agents operate using a ~100-fold lower concentration of gadolinium ions in comparison to the necessary concentration of iodine employed in CT imaging. Herein, we describe some of the general potential directions of macromolecular MRI contrast agents using our recently reported families of dendrimer-based agents as examples. Changes in molecular size altered the route of excretion. Smaller-sized contrast agents less than 60 kDa molecular weight were excreted through the kidney resulting in these agents being potentially suitable as functional renal contrast agents. Hydrophilic and larger-sized contrast agents were found better suited for use as blood pool contrast agents. Hydrophobic variants formed with polypropylenimine diaminobutane dendrimer cores created liver contrast agents. Larger hydrophilic agents are useful for lymphatic imaging. Finally, contrast agents conjugated with either monoclonal antibodies or with avidin are able to function as tumor-specific contrast agents, which also might be employed as therapeutic drugs for either gadolinium neutron capture therapy or in conjunction with radioimmunotherapy.

A novel approach to the microdosimetry of neutron capture therapy. Part I. High-resolution quantitative autoradiography applied to microdosimetry in neutron capture therapy

International Nuclear Information System (INIS)

Solares, G.R.; Zamenhof, R.G.

1995-01-01

A novel approach to the microdosimetry of neutron capture therapy has been developed using high-resolution quantitative autoradiography (HRQAR) and two-dimensional Monte Carlo simulation. This approach has been applied using actual cell morophology (nuclear and cytoplasmic cell structures) and the measured microdistribution of boron-10 in a transplanted murine brain tumor (GL261) containing p-boronophenylalanine (BPA) as the boron compound. The 2D Monte Carlo transport code for the α and 7 Li charged particles from the 10 B(n,α) 7 Li reactions has been developed as a surrogate to a full 3D approach to calculate a variety of different microdosimetric parameters. The HRQAR method and the surrogate 2D Monte Carlo approach are described in detail and examples of their use are presented. 27 refs., 11 figs., 1 tab

Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies? A systematic review.

Science.gov (United States)

Polak, David; Martin, Conchita; Sanz-Sánchez, Ignacio; Beyth, Nurit; Shapira, Lior

2015-04-01

Systematically review the scientific evidence for efficiency of anti-inflammatory agents against gingivitis, either as solo treatments or adjunctive therapies. A protocol was developed aimed to answer the following focused question: "Are anti-inflammatory agents effective in treating gingivitis as solo or adjunct therapies?" RCTs and cohort studies on anti-inflammatory agents against gingivitis studies were searched electronically. Screening, data extraction and quality assessment were conducted. The primary outcome measures were indices of gingival inflammation. A sub-analysis was performed dividing the active agents into anti-inflammatory and other drugs. The search identified 3188 studies, of which 14 RCTs met the inclusion criteria. The use of anti-inflammatory or other agents, in general showed a higher reduction in the test than in the control in terms of gingival indexes and bleeding scores. Only two RCTs on inflammatory drugs could be meta-analysed, showing a statistically significant reduction in the GI in the experimental group [WMD = -0.090; 95% CI (-0.105; -0.074); p = 0.000]. However, the contribution of both studies to the global result was unbalanced (% weight: 99.88 and 0.12 respectively). Most of the tested material showed beneficial effect as anti-inflammatory agents against gingivitis, either as a single treatment modality or as an adjunctive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Osteoarthritis: Key elements in its pathogenesis and current agents for pathogenetic therapy

Directory of Open Access Journals (Sweden)

Yu. A. Olyunin

2017-01-01

Full Text Available Three main areas can be arbitrarily identified in the modern concept of treatment for osteoarthritis (OA; these are: 1 an impact on the progression of joint destruction; 2 suppression of peripheral pain mechanisms; and 3 inhibition of the central processes involved in the formation of pain sensation. Glucosamine and chondroitin sulfate (CS have become the first agents that are able to retard the development of cartilage degeneration. They have been used in medical practice for more than 40 years. A number of clinical trials of these drugs have yielded favorable results during their use in patients with OA. Another agent containing amino sugars and CS – sea fish cartilage hydrolysate has more recently emerged. Clinical trials have demonstrated that it is able to significantly relieve OA-induced pain. To date, the main agent for the analgesic therapy of OA is considered to be nonsteroidal anti-inflammatory drugs (NSAIDs that act on the peripheral mechanisms of pain and are widely used to treat diseases that are accompanied by chronic pain. However, a large-scale meta-analysis dealing with the experience with NSAIDs used to treat OA has shown that pain relief due to this therapy averaged only about 10 mm on a 100-mm visual analogue scale. To enhance the efficiency of therapy for OA, drug and non-drug treatments that affect the central mechanisms of pain in this disease are also used.

Monte Carlo assessment of boron neutron capture therapy for the treatment of breast cancer

Directory of Open Access Journals (Sweden)

Mundy Daniel W.

2005-01-01

Full Text Available For a large number of women who are diagnosed with breast cancer every year the avail able treatment options are effective, though physically and mentally taxing. This work is a starting point of a study of the efficacy of boron neutron capture therapy as an alternative treatment for HER-2+ breast tumors. Using HER-2-specific monoclonal anti bodies coupled with a boron-rich oligomeric phosphate diester, it may be possible to deliver sufficient amounts of 10B to a tumor of the breast to al low for selective cell destruction via irradiation by thermal neutrons. A comprehensive computational model (MCNP for thermal neutron irradiation of the breast is described, as well as the results of calculations made using this model, in order to determine the optimum boron concentration within the tumor for an effective boron neutron capture therapy treatment, as compared with traditional X-ray radiotherapy. The results indicate that a boron concentration of 50-60 mg per gram of tumor tissue is optimal when considering treatment times, dose distributions and skin sparing. How ever these results are based upon best-guess assumptions that must be experimentally verified.

Dose Determination using alanine detectors in a Mixed Neutron and Gamma Field for Boron Neutron Capture Therapy of Liver Malignancies

DEFF Research Database (Denmark)

Schmitz, T.; Blaickner, M.; Ziegner, M.

2011-01-01

Introduction Boron Neutron Capture Therapy for liver malignancies is being investigated at the University of Mainz. One important aim is the set-up of a reliable dosimetry system. Alanine dosimeters have previously been applied for dosimetry of mixed radiation fields in antiproton therapy, and ma...

Nominal effective radiation doses delivered during clinical trials of boron neutron capture therapy

International Nuclear Information System (INIS)

Capala, J.; Diaz, A.Z.; Chanana, A.D.

1997-01-01

Boron neutron capture therapy (BNCT) is a binary system that, in theory, should selectively deliver lethal, high linear energy transfer (LET) radiation to tumor cells dispersed within normal tissues. It is based on the nuclear reaction 10-B(n, α)7-Li, which occurs when the stable nucleus of boron-10 captures a thermal neutron. Due to the relatively high cross-section of the 10-B nucleus for thermal neutron capture and short ranges of the products of this reaction, tumor cells in the volume exposed to thermal neutrons and containing sufficiently high concentration of 10-B would receive a much higher radiation dose than the normal cells contained within the exposed volume. Nevertheless, radiation dose deposited in normal tissue by gamma and fast neutron contamination of the neutron beam, as well as neutron capture in nitrogen, 14-N(n,p)14-C, hydrogen, 1-H(n,γ)2-H, and in boron present in blood and normal cells, limits the dose that can be delivered to tumor cells. It is, therefore, imperative for the success of the BNCT the dosed delivered to normal tissues be accurately determined in order to optimize the irradiation geometry and to limit the volume of normal tissue exposed to thermal neutrons. These are the major objectives of BNCT treatment planning

Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

Science.gov (United States)

Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

2004-06-01

Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been able to image the subcellular distribution of gadolinium-157, as well as the other six naturally abundant isotopes of gadolinium, with SIMS ion microscopy. T98G human glioblastoma cells were treated for 24 h with 25 mg/ml of the metal ion complex diethylenetriaminepentaacetic acid Gd(III) dihydrogen salt hydrate (Gd-DTPA). Gd-DTPA is a contrast enhancing agent used for MRI of brain tumors, blood-brain barrier impairment, diseases of the central nervous system, etc. A highly heterogeneous subcellular distribution was observed for gadolinium-157. The nuclei in each cell were distinctly lower in gadolinium-157 than in the cytoplasm. Even within the cytoplasm the gadolinium-157 was heterogeneously distributed. The other six naturally abundant isotopes of gadolinium were imaged from the same cells and exhibited a subcellular distribution consistent with that observed for gadolinium-157. These observations indicate that SIMS ion microscopy may be a viable approach for subcellular studies of gadolinium containing neutron capture therapy drugs and may even play a major role in the development and validation of new gadolinium contrast enhancing agents for diagnostic MRI applications.

Evaluation of hypoxia-specific cytotoxic bioreductive agent-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy

International Nuclear Information System (INIS)

Masunaga, Shin-ichiro; Nagasawa, Hideko; Gotoh, Keiko

2006-01-01

The purpose of this study was to evaluate the usefulness of 5 new 10 B-compounds (TX-2091, TX-2095, TX-2097, TX-2100, and TX-2110) as 10 B-carriers in boron neutron capture therapy (BNCT). They were conjugates that had been synthesized from a hypoxia-specific cytotoxic bioreductive agent, quinoxaline oxide TX-402, and a clinically used 10 B-carrier, sodium borocaptate- 10 B (BSH). The 5 new compounds were hybrid compounds that have both a hypoxic cytotoxin unit and a thermal neutron-sensitizing unit, BSH. These new compounds and BSH were administered intraperitoneally to SCC VII tumor-bearing mice. Then, the 10 B concentrations in the tumors and normal tissues were measured by γ-ray spectrometry. Subsequently, SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with TX-2100, which was chosen based on the results of the above-mentioned biodistribution analyses, or BSH in the same manner as in the biodistribution studies. Right after irradiation, during which intratumor 10 B concentrations were kept at levels similar to each other, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling [=quiescent (Q) cells] was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in the total (P+Q) tumor cell population was determined from the tumors that were not pretreated with BrdU. Clonogenic cell survival was also determined in mice given no BrdU. 10 B biodistribution analyses in tumors, brain, skin, muscles, blood, and liver indicated that TX-2100 has the most favorable characteristics for concentrating a sufficient amount of 10 B in tumors and maintaining a high enough 10 B concentration during irradiation. In addition, TX-2100 had a significantly stronger radio-sensitizing effect with

Physical engineering and medical physics on boron neutron capture therapy

International Nuclear Information System (INIS)

Sakurai, Yoshinori

2011-01-01

The contents of physical engineering and medical physics that support boron neutron capture therapy (BNCT) can be roughly classified to the four items, (1) neutron irradiation system, (2) development and improvement of dose assessment techniques, (3) development and improvement of dose planning system, and (4) quality assurance and quality control. This paper introduces the BNCT at Kyoto University Research Reactor Institute, with a focus on the basic physics of BNCT, thermal neutron irradiation and epithermal neutron irradiation, heavy water neutron irradiation facilities of KUR, and medical irradiation system of KUR. It also introduces the world's first BNCT clinical cyclotron irradiation system (C-BENS) of Kyoto University Research Reactor Institute, BNCT dose assessment techniques, dose planning system, and quality assurance and quality control. (A.O.)

Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer

Directory of Open Access Journals (Sweden)

Barth Rolf F

2012-08-01

Full Text Available Abstract Boron neutron capture therapy (BNCT is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non-radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high grade gliomas, recurrent cancers of the head and neck region and either primary or metastatic melanoma. Neutron sources for BNCT currently have been limited to specially modified nuclear reactors, which are or until the recent Japanese natural disaster, were available in Japan, United States, Finland and several other European countries, Argentina and Taiwan. Accelerators producing epithermal neutron beams also could be used for BNCT and these are being developed in several countries. It is anticipated that the first Japanese accelerator will be available for therapeutic use in 2013. The major hurdle for the design and synthesis of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations in the range of 20 μg/g. This would be sufficient to deliver therapeutic doses of radiation with minimal normal tissue toxicity. Two boron drugs have been used clinically, a dihydroxyboryl derivative of phenylalanine, referred to as boronophenylalanine or “BPA”, and sodium borocaptate or “BSH” (Na2B12H11SH. In this report we will provide an overview of other boron delivery agents that currently are under evaluation, neutron sources in use or under development for BNCT, clinical dosimetry, treatment planning, and finally a summary of previous and on-going clinical studies for high grade gliomas and recurrent tumors of the head and neck region. Promising results have been obtained with both groups of patients but these outcomes must be more rigorously evaluated in larger

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Directory of Open Access Journals (Sweden)

Kamal SM

2014-06-01

Full Text Available Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL

Boron thermal/epithermal neutron capture therapy

International Nuclear Information System (INIS)

Fairchild, R.G.

1982-01-01

The development of various particle beams for radiotherapy represents an attempt to improve dose distribution, and to provide high LET radiations which are less sensitive to ambient physical and radiobiological factors such as oxygen tension, cell cycle, and dose rate. In general, a compromise is necessary as effective RBE is reduced in order to spread the dose distribution over the anticipated tumor volume. The approach of delivering stable non-toxic isotopes to tumor, and then activating these atoms subsequently via an external radiation beam has mator advantages; problems associated with high uptake of these isotopes in competing cell pools are obviated, and the general tumor volume can be included in the treatment field of the activating beam. As long as the normal tissues supporting tumor show a low uptake of the isotope to be activated, and as long as the range of the reaction products is short, dose will be restricted to tumor, with a consequent high therapeutic ratio. Neutron Capture Therapy (NCT) is generally carried out by activating boron-10 with low energy neutrons. The range of the high LET, low OER particles from the 10 B(n, α) 7 Li reaction is approx. 10μ, or one cell diameter, a situation that is optimal for cell killing. Significant advantages may be gained by using the NCT procedure in conjunction with improved tissue penetration provided with epithermal or filtered beams, and new compounds showing physiological binding to tumor

Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

OpenAIRE

Wang, Peng; Zhen, Haining; Jiang, Xinbiao; Zhang, Wei; Cheng, Xin; Guo, Geng; Mao, Xinggang; Zhang, Xiang

2010-01-01

Abstract Background Boron neutron capture therapy (BNCT) is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE) of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR) and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical Un...

The Effects of Glucose Therapy Agents-Apple Juice, Orange Juice, and Cola-on Enteral Tube Flow and Patency.

Science.gov (United States)

Steinberg, Daphna J; Montreuil, Jasmine; Santoro, Andrea L; Zettas, Antonia; Lowe, Julia

2016-06-01

To develop evidence-based hypoglycemia treatment protocols in patients receiving total enteral nutrition, this study determined the effect on enteral tube flow of glucose therapy agents: apple juice, orange juice, and cola, and it also examined the effects of tube type and feed type with these glucose therapy agents. For this study, 12 gastrostomy tubes (6 polyethylene and 6 silicone) were set at 50 mL/h. Each feeding set was filled with Isosource HN with fibre or Novasource Renal. Each tube was irrigated with 1 glucose therapy agent, providing approximately 20 g of carbohydrate every 4 h. Flow-rate measurements were collected at 2 h intervals. The results showed that the glucose therapy agent choice affected flow rates: apple juice and cola had higher average flow rates than orange juice (P = 0.01). A significant difference was found between tube type and enteral formula: polyethylene tubes had higher average flow rates than silicone tubes (P orange juice, and thus may be considered as primary treatment options for hypoglycemia in enterally fed patients. Polyethylene tubes and Isosource HN with fibre were less likely to clog than silicone tubes and Novasource Renal.

Boron-containing thioureas for neutron capture therapy

International Nuclear Information System (INIS)

Ketz, H.

1993-01-01

Melanin is produced in large amounts in malignant melanotic melanomas. Because thiourea compounds are covalently incorporated into melanin during its biosynthesis, the preparation of boronated thiourea-derivatives is of particular interest for the BNCT (Boron Neutron Capture Therapy). Accumulation of boron in tumors by means of boronated thiourea-derivatives may therefore provide levels of 10 B which are useful for BNCT. In BNCT the tumor containing the boron compound is irradiated with epithermal neutrons to generate He- and Li-nuclei from the 10 B which can then destroy the tumor cells. Because of the short ranges of these particles (approximately one cell diameter) the damage will be almost exclusively confined to the tumor leaving normal tissue unharmed. High accumulation of 2-mercapto-1-methylimidazole (methimazole) in melanotic melanomas has been described in the literature. Boronated derivatives of methimazole were therefore synthesized. Boron was in the form of a boronic acid, a nido-carbonate and a mercaptoundeca hydro-closo-dodecaborate (BSH). The synthesis of the boron cluster derivatives of methimazole (nido-carborate- and BSH-derivatives) with 9 resp. 12 boron atoms in the molecule were expected to achieve higher concentrations of boron in the tumor than in the case of the boronic acid compound with its single boron atom. (orig.) [de

Single photon image from PET with insertable collimator for boron neutron capture therapy

International Nuclear Information System (INIS)

Jung, Jooyoung; Suh, Tae Suk; Hong, Key Jo

2014-01-01

Boron neutron capture therapy (BNCT) is a radiation therapy technique for treating deep-seated brain tumors by irradiation with a thermal neutron in which boron-labelled low molecular weight compounds. Once completed, a single photon emission computed tomography (SPECT) scan is conducted to investigate for the region of therapy using an isotope exclusive to SPECT. In the case of an existing PET/SPECT combination system, at least two types of isotopes should be used for each scan with their purposes. Recently, researchers examined the effects of PET/SPECT dual modality on animal imaging systems. They reported that the PET/SPECT combination system was effective for simultaneous achievement of a single event and coincidence. The aim of our proposed system is to confirm the feasibility of extraction of two types of images from one PET module with an insertable collimator for brain tumor treatment during the BNCT. We attempted to acquire the PET and SPECT images simultaneously using only PET without an additional isotope. Single photon images were acquired using an insertable collimator on a PET detector

Improvement of JCDS, a computational dosimetry system in JAEA for neutron capture therapy

International Nuclear Information System (INIS)

Kumada, Hiroaki; Yamamoto, Kazuyoshi; Matsumura, Akira; Yamamoto, Tetsuya; Nakagawa, Yoshinobu; Kageji, Teruyoshi

2006-01-01

JCDS, a computational dosimetry system for neutron capture therapy, was developed by Japan Atomic Energy Agency. The system has been sophisticated to facilitate dose planning so far. In dosimetry with JCDS for BNCT clinical trials at JRR-4, several absorbed doses and the dose distributions are determined by a voxel model consisted of 2x2x2mm 3 voxel cells. By using the detailed voxel model, accuracy of the dosimetry can be improved. Clinical trials for melanoma and head-and-neck cancer as well as brain tumor were started using hot version of JCDS in 2005. JCDS is also being of improved so as to enable a JCDS application to dosimetry by PHITS as well as dosimetry by MCNP. By using PHITS, total doses of a patient by a combined modality therapy, for example a combination of BNCT and proton therapy, can be estimated consistently. Moreover, PET images can be adopted in combination with CT and MRI images as a farsighted approach. JCDS became able to identify target regions by using the PET values. (author)

A comparison of the COG and MCNP codes in computational neutron capture therapy modeling, Part II: gadolinium neutron capture therapy models and therapeutic effects.

Science.gov (United States)

Wangerin, K; Culbertson, C N; Jevremovic, T

2005-08-01

The goal of this study was to evaluate the COG Monte Carlo radiation transport code, developed and tested by Lawrence Livermore National Laboratory, for gadolinium neutron capture therapy (GdNCT) related modeling. The validity of COG NCT model has been established for this model, and here the calculation was extended to analyze the effect of various gadolinium concentrations on dose distribution and cell-kill effect of the GdNCT modality and to determine the optimum therapeutic conditions for treating brain cancers. The computational results were compared with the widely used MCNP code. The differences between the COG and MCNP predictions were generally small and suggest that the COG code can be applied to similar research problems in NCT. Results for this study also showed that a concentration of 100 ppm gadolinium in the tumor was most beneficial when using an epithermal neutron beam.

Neutron spectrum for neutron capture therapy in boron; Espectro de neutrones para terapia por captura de neutrones en boro

Energy Technology Data Exchange (ETDEWEB)

Medina C, D.; Soto B, T. G. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Programa de Doctorado en Ciencias Basicas, 98068 Zacatecas, Zac. (Mexico); Baltazar R, A. [Universidad Autonoma de Zacatecas, Unidad Academica de Ingenieria Electrica, Programa de Doctorado en Ingenieria y Tecnologia Aplicada, 98068 Zacatecas, Zac. (Mexico); Vega C, H. R., E-mail: dmedina_c@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico)

2016-10-15

Glioblastoma multiforme is the most common and aggressive of brain tumors and is difficult to treat by surgery, chemotherapy or conventional radiation therapy. One treatment alternative is the Neutron Capture Therapy in Boron, which requires a beam modulated in neutron energy and a drug with {sup 10}B able to be fixed in the tumor. When the patients head is exposed to the neutron beam, they are captured by the {sup 10}B and produce a nucleus of {sup 7}Li and an alpha particle whose energy is deposited in the cancer cells causing it to be destroyed without damaging the normal tissue. One of the problems associated with this therapy is to have an epithermal neutrons flux of the order of 10{sup 9} n/cm{sup 2}-sec, whereby irradiation channels of a nuclear research reactor are used. In this work using Monte Carlo methods, the neutron spectra obtained in the radial irradiation channel of the TRIGA Mark III reactor are calculated when inserting filters whose position and thickness have been modified. From the arrangements studied, we found that the Fe-Cd-Al-Cd polyethylene filter yielded a ratio between thermal and epithermal neutron fluxes of 0.006 that exceeded the recommended value (<0.05), and the dose due to the capture gamma rays is lower than the dose obtained with the other arrangements studied. (Author)

Radiobiology of boron neutron capture therapy

International Nuclear Information System (INIS)

Bond, V.P.

1986-01-01

The author addresses the question of single session versus protracted therapy in the application of boron neutron therapy to tumors. As background he discusses the reasoning behind the current use of fractionated therapy with conventional low-LET radiations and difference which may obtain for neutron therapy. Several aspects of dose rates and dose levels are then addressed

A new target concept for proton accelerator driven boron neutron capture therapy applications

International Nuclear Information System (INIS)

Powell, J.R.; Ludewig, H.; Todosow, M.; Reich, M.

1998-01-01

A new target concept termed Discs Incorporating Sector Configured Orbiting Sources (DISCOS), is proposed for spallation applications, including BNCT (Boron Neutron Capture Therapy). In the BNCT application a proton beam impacts a sequence of ultra thin lithium DISCOS targets to generate neutrons by the 7 Li(p,n) 7 Be reaction. The proton beam loses only a few keV of its ∼MeV energy as it passes through a given target, and is re-accelerated to its initial energy, by a DC electric field between the targets

Targeted therapies for diarrhea-predominant irritable bowel syndrome

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Olden KW

2012-05-01

Full Text Available Kevin W OldenDepartment of Medicine, St Joseph's Hospital and Medical Center, Phoenix, AZ, USAAbstract: Irritable bowel syndrome (IBS causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients' daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1 for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized

Proceedings of workshop on 'boron chemistry and boron neutron capture therapy'

International Nuclear Information System (INIS)

Kitaoka, Yoshinori

1993-09-01

This volume contains the proceedings of the 5th Workshop on 'the Boron Chemistry and Boron Neutron Capture Therapy' held on February 22 in 1993. The solubility of the boron carrier play an important role in the BNCT. New water-soluble p-boronophenylalanine derivatives are synthesized and their biological activities are investigated (Chap. 2 and 3). Some chemical problems on the BNCT were discussed, and the complex formation reaction of hydroxylboryl compounds were studied by the paper electrophoresis (Chap. 4). The results of the medical investigation on the BNCT using BSH compounds are shown in Chap. 5. Syntheses of o- and m-boronophenylalanine were done and their optical resolution was tried (Chap. 6). The complex formation reaction of p-boronophenylalanine (BPA) with L-DOPA and the oxidation reaction of the analogs are found in Chap. 7. The pka of BPA were determined by the isotachophoresis (Chap. 8). The chemical nature of dihydroxyboryl compounds were investigated by an infrared spectroscopy and electrophoresis (Chap. 9). New synthetic methods of BPA and p-boronophenylserine using ester of isocyanoacetic acid are described in Chap. 10. The induction of chromosomal aberations by neutron capture reaction are discussed from a point of the biological view. The a of the presented papers are indexed individually. (J.P.N.)

Boron neutron capture therapy combined with fractionated photon irradiation for glioblastoma: A recursive partitioning analysis of BNCT patients

International Nuclear Information System (INIS)

Nakai, K.; Yamamoto, T.; Aiyama, H.; Takada, T.; Yoshida, F.; Kageji, T.; Kumada, H.; Isobe, T.; Endo, K.; Matsuda, M.; Tsurubuchi, T.; Shibata, Y.; Takano, S.; Mizumoto, M.; Tsuboi, K.; Matsumura, A.

2011-01-01

Eight patients to received Boron Neutron Capture Therapy (BNCT) were selected from 33 newly diagnosed glioblastoma patients (NCT(+) group). Serial 42 glioblastoma patients (NCT(−) group) were treated without BNCT. The median OS of the NCT(+) group and NCT (−) group were 24.4 months and 14.9 months. In the high risk patients (RPA class V), the median OS of the NCT(+) group tended to be better than that of NCT(−) group. 50% of BNCT patients were RPA class V. - Highlights: ► We treated 8 patients with boron neutron capture therapy (NCT) for glioblastoma. ► We compare the overall survival between NCT including series and without NCT series. ► The median overall survival of the NCT including series was 24.4 months. ► In the high risk patients, the median OS of NCT including series tended to be better.

Design study of a medical reactor for Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Sasaki, M.; Hirota, J.; Tamao, S.; Kanda, K.; Mishima, Y.

1992-01-01

A new design study of a medical reactor for Boron Neutron Capture Therapy (BNCT) has been carried out. The reactor is to be used exclusively for the treatment of malignant melanoma and other cancers as well as for the further biomedical research. Main specifications of the reactor are as follows; thermal power of 2 MW, water cooling by natural convection, semitight core of triangular lattice, UO 2 fuel rod of 9.5 mm diameter and no refueling in the reactor-life. Three horizontal and one vertical neutron beam hole are to be provided to deliver thermal and epithermal neutrons. N-γ coupling Sn transport calculations indicate that the patient treatment period will be about 30 minutes with minimal fast neutron and gamma contaminants. (author)

Boron neutron capture therapy for malignant brain tumor and future potential

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Hatanaka, Hiroshi.

1994-01-01

This paper presents therapeutic experience with boron neutron capture therapy (BNCT) for malignant brain tumors. Nine patients who survived for 10 years or more as of 1986 are given in a table. A review of the 9 patients concluded that physical dose of 15 Gy is required. In addition, the following factors are defined to be the most important: (1) to determine tumor size and depth as accurately as possible, (2) to measure neutron doses in the deepest site of the tumor during irradiation, (3) to measure the content of boron within the tumor, and to deliver neutron beams as deeply as possible. Finally, the importance of knowing RBE of alpha particles for tumor cells of the human brain is emphasized. (N.K.)

A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

Directory of Open Access Journals (Sweden)

Xu L

2016-07-01

Full Text Available Liang Xu,1,2,* Xiaobo Wu,3,* Chun Hu,1,2 Zhiying Zhang,4 Le Zhang,1,2 Shujing Liang,1,2 Yingchun Xu,5 Fengchun Zhang1,2 1Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, 2Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 3Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang, 4Graduate School, Xuzhou Medical College, Xuzhou, 5Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nowadays, the philosophy of treating metastatic breast cancer (MBC is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015 comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS, and the secondary end points were the progression-free survival (PFS, overall response rate (ORR, and grade 3 or 4 toxicities. The pooled hazard ratio (HR and pooled risk ratio (RR were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002, PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001, and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001. Notably, subgroup analysis

Computational Dosimetry and Treatment Planning Considerations for Neutron Capture Therapy

International Nuclear Information System (INIS)

Nigg, David Waler

2003-01-01

Specialized treatment planning software systems are generally required for neutron capture therapy (NCT) research and clinical applications. The standard simplifying approximations that work well for treatment planning computations in the case of many other modalities are usually not appropriate for application to neutron transport. One generally must obtain an explicit three-dimensional numerical solution of the governing transport equation, with energy-dependent neutron scattering completely taken into account. Treatment planning systems that have been successfully introduced for NCT applications over the past 15 years rely on the Monte Carlo stochastic simulation method for the necessary computations, primarily because of the geometric complexity of human anatomy. However, historically, there has also been interest in the application of deterministic methods, and there have been some practical developments in this area. Most recently, interest has turned toward the creation of treatment planning software that is not limited to any specific therapy modality, with NCT as only one of several applications. A key issue with NCT treatment planning has to do with boron quantification, and whether improved information concerning the spatial biodistribution of boron can be effectively used to improve the treatment planning process. Validation and benchmarking of computations for NCT are also of current developmental interest. Various institutions have their own procedures, but standard validation models are not yet in wide use

Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy.

Science.gov (United States)

Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

2016-01-01

Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics.

Rituximab, alkylating agents or combination therapy for gastric mucosa-associated lymphoid tissue lymphoma: a monocentric non-randomised observational study.

Science.gov (United States)

Amiot, A; Lévy, M; Copie-Bergman, C; Dupuis, J; Szablewski, V; Le Baleur, Y; Baia, M; Belhadj, K; Sobhani, I; Leroy, K; Haioun, C; Delchier, J-C

2014-03-01

There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). After a median follow-up period of 4.9 years (range 0.4-17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P alkylating agents alone. Rituximab has a better safety profile than regimens containing alkylating agents. © 2014 John Wiley & Sons Ltd.

Slow-neutron capture therapy for malignant tumours: its history and recent development

International Nuclear Information System (INIS)

Hatanaka, H.

1975-01-01

Slow-neutron capture therapy was first suggested in 1936. The early clinical trials were performed at Brookhaven National Laboratory and Massachusetts Institute of Technology reactors. In the last series of treatments in 1960 and 1961, none of the 17 glioblastoma patients lived longer than a year and the clinical trial was discontinued, particularly because the was pathological evidence that normal tissue had been seriously damaged. Hatanaka, who worked first with Sweet between 1964 and 1967, continued intensive basic research and organized a collaborating team of chemists, physicists and physicians in Japan where he resumed treatment of brain tumour patients in 1968. The rationale of the revised therapy included: (1) use of promising compounds such as mercaptoundecahydrododecaborate, which has a high tumour binding property, (2) use of adrenocorticoid to minimize vascular damage, (3) intra-arterial infusion of boron to obtain a higher concentration in the tumour, (4) restriction of excessive neutron intensity, (5) and some technical improvements. New research techniques were also introduced, such as alpha autoradiography, electron microscopy, and immunotherapy. With the mercaptoundecahydrododecaborate compound an absolute concentration of 30 μg per gram of tumour is easily attainable, while the blood level of the isotope can be lowered to at least half of the tumour concentration. Normal dog brains were able to tolerate this therapy. Among the 15 patients so far treated, 13 were treated at the Hitachi Training Reactor. Patients, who had undergone repeated surgery as well as excessive irradiation before they came for the therapy, could not recover their full activities, but proved they could enjoy a significant prolongation of their lives. The only two fresh cases of glioblastoma responded so well to the therapy that one has been working as an engineer and the other as a farmer for 3 years without neurological deficits. Recent progress and future potentials of the

Boron neutron capture therapy for advanced and/or recurrent cancers in the oral cavity

International Nuclear Information System (INIS)

Ariyoshi, Yasunori; Shimahara, Masashi; Kimura, Yoshihiro; Miyatake, Shin-ichi; Kuroiwa, Toshihiko; Nagata, Kenji; Sakurai, Yoshinori; Maruhashi, Akira; Ono, Koji

2006-01-01

This preliminary study of 5 patients with advanced and/or recurrent cancer in the oral cavity was performed to evaluate the effectiveness of Boron Neutron Capture Therapy (BNCT). The patients received therapy with the 10 B-carrier p-boronophenylalanine (BPA) with or without borocaptate sodium (BSH) and irradiation thereafter with epithermal neutrons. All underwent 18 F-BPA PET studies before receiving BNCT to determine the accumulation ratios of BPA in tumor and normal tissues. The tumor mass was decreased in size and at minimum a transient partial response was achieved in all cases, though rapid tumor re-growth was observed in 2. Although tentative clinical responses and improvements in quality of life were recognized, obliteration of the tumor was not obtained in any of the cases. Additional studies are required to determine the utility and indication of BNCT for oral cancer. (author)

External Qi therapy to treat symptoms of Agent Orange Sequelae in Korean combat veterans of the Vietnam War.

Science.gov (United States)

Lee, Myeong Soo; Woo, Won-Hong; Lim, Hyun-Ja; Hong, Sung-Soo; Kim, Hye-Jung; Moon, Sun-Rock

2004-01-01

We investigated the efficacy of Qi therapy as a non-pharmacological treatment for various symptoms presented by Korean combat veterans of the Vietnam War with Agent Orange Sequelae. Nine subjects volunteered to receive 30 minutes of Qi therapy, twice per day for 7 days. There was marked improvement in 89% of the patients with impaired physical activity, 86% of those with psychological disorder, 78% of those with heavy drug use, and 67% of those with fatigue, indigestion and high blood glucose levels. This data suggests that Qi therapy combined with conventional treatment has positive effects in reducing and managing the pain, psychosomatic disorders, and substance abuse in patients with Agent Orange Sequelae. We cannot completely discount the possible influence of the placebo effect, and more objective, clinical measures are needed to study the long-term effects of Qi therapy.

Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

Energy Technology Data Exchange (ETDEWEB)

A. Monti Hughes; ECC Pozzi; S. Thorp; M. A. Garabalino; R. O. Farias; S. J. Gonzalez; E. M. Heber; M. E. Itoiz; R. F. Aromando; A. J. Molinari; M. Miller; D. W. Nigg; P. Curotto; V. A. Trivillin; A. E. Schwint

2013-11-01

Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.

Multi-Family Pediatric Pain Group Therapy: Capturing Acceptance and Cultivating Change

Directory of Open Access Journals (Sweden)

Samantha E. Huestis

2017-12-01

Full Text Available Behavioral health interventions for pediatric chronic pain include cognitive-behavioral (CBT, acceptance and commitment (ACT, and family-based therapies, though literature regarding multi-family therapy (MFT is sparse. This investigation examined the utility and outcomes of the Courage to Act with Pain: Teens Identifying Values, Acceptance, and Treatment Effects (CAPTIVATE program, which included all three modalities (CBT, ACT, MFT for youth with chronic pain and their parents. Program utility, engagement, and satisfaction were evaluated via quantitative and qualitative feedback. Pain-specific psychological, behavioral, and interpersonal processes were examined along with outcomes related to disability, quality of life, pain interference, fatigue, anxiety, and depressive symptoms. Participants indicated that CAPTIVATE was constructive, engaging, and helpful for social and family systems. Clinical and statistical improvements with large effect sizes were captured for pain catastrophizing, acceptance, and protective parenting but not family functioning. Similar effects were found for functional disability, pain interference, fatigue, anxiety, and depression. Given the importance of targeting multiple systems in the management of pediatric chronic pain, preliminary findings suggest a potential new group-based treatment option for youth and families. Next steps involve evaluating the differential effect of the program over treatment as usual, as well as specific CBT, ACT, and MFT components and processes that may affect outcomes.

The implication of decorporation therapy for contaminated persons

International Nuclear Information System (INIS)

Matsuoka, Osamu

1989-01-01

The procedures of removal on internally deposited radionuclides from accidentally contaminated individual are divided for two different category such as 1) Physical procedure, and 2) Chemical procedure. Physical procedures include surgical excision and lung lavage. Both procedures are very effective for decorporation but are slight unsafe in procedure itself. Therefore, it is difficult to judge to apply these procedures under balance of risk and benefit. Chemical procedure include 1) Inhibition of intestinal absorption, such as production of insoluble compounds. 2) Capture of radionuclides in entero-hepatic circulation such as Cs-137 by Prussian Blue, 3) Blocking of deposition to target organs or competitive acceleration of excretion by excess administration of stable isotope or analogous element such as stable iodine for thyroid blocking and 4) Acceleration of excretion by chelating agent such as Pb by EDTA, Hg by BAL, Fe by DFOA. Chelation therapy is major procedure of most practical sense. For the removal of transuranic element, Ca-DTPA and Zn-DTPA (1g/day/person) are the most effective agents in conventional use and new developing agent such as TTHA, Puchel and LICAMS are still not in routine use. The advantage and disadvantage of each agent for decorporation therapy were reviewed. The future research trends expected were discussed related with current difficulties on the application of chelating therapy. (author)

Clinical results of boron neutron capture therapy (BNCT) for glioblastoma

International Nuclear Information System (INIS)

Kageji, T.; Mizobuchi, Y.; Nagahiro, S.; Nakagawa, Y.; Kumada, H.

2011-01-01

The purpose of this study was to evaluate the clinical outcome of BSH-based intra-operative BNCT (IO-BNCT) and BSH and BPA-based non-operative BNCT (NO-BNCT). We have treated 23 glioblastoma patients with BNCT without any additional chemotherapy since 1998. The median survival time (MST) of BNCT was 19.5 months, and 2-year, 3-year and 5-year survival rates were 26.1%, 17.4% and 5.8%, respectively. This clinical result of BNCT in patients with GBM is superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment. - Highlights: ► In this study, we evaluate the clinical outcome of boron neutron capture therapy (BNCT) for malignant brain tumors. ► We have treated 23 glioblastoma (GBM) patients with BNCT without any additional chemotherapy. ► Clinical results of BNCT in patients with GBM are superior to that of single treatment of conventional radiotherapy compared with historical data of conventional treatment.

Improved evaluation of antivascular cancer therapy using constrained tracer-kinetic modeling for multi-agent dynamic contrast-enhanced MRI

NARCIS (Netherlands)

Hectors, Stefanie; Jacobs, Igor; Lok, Jasper; Peters, Johannes; Bussink, Johan; Hoeben, Freek J. M.; Keizer, Henk; Janssen, Henk M.; Nicolay, Klaas; Schabel, Matthias; Strijkers, Gustav

2018-01-01

Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of tumor vasculature to anti-vascular therapies. Multi-agent DCE-MRI employs a combination of low and high molecular weight contrast agents, which potentially improves the accuracy of estimation of tumor

Clinical treatment planning for subjects undergoing boron neutron capture therapy at Harvard-MIT

International Nuclear Information System (INIS)

Zamenhof, R.G.; Palmer, M.R.; Buse, P.M.

2001-01-01

Treatment planning is a crucial component of the Harvard-MIT boron neutron capture therapy (BNCT) clinical trials. Treatment planning can be divided into five stages: (1) pre-planning, based on CT and MRI scans obtained when the subject arrives at the hospital and on assumed boron-10 distribution parameters; (2) subject set-up, or simulation, in the MITR-II medical therapy room to determine the boundary conditions for possible set-up configurations; (3) re-planning, following the subject simulation; (4) final localization of the subject in the medical therapy room for BNCT; and (5) final post facto recalculation of the doses delivered based on firm knowledge of the blood boron-10 concentration profiles and the neutron flux histories from precise online monitoring. The computer-assisted treatment planning is done using a specially written BNCT treatment planning code called MacNCTPLAN. The code uses the Los Alamos National Laboratory's Monte Carlo n-particle radiation transport code MCNPv.4b as the dose calculation engine and advanced anatomical model simulation based on an automatic evaluation of CT scan data. Results are displayed as isodose contours and dose-volume histograms, the latter correlated precisely with corresponding anatomical CT or MRI image planes. Examples of typical treatment planning scenarios will be presented. (author)

The Idaho Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program overview

International Nuclear Information System (INIS)

Dorn, R.V. III; Griebenow, M.L.; Ackermann, A.L.; Miller, L.G.; Miller, D.L.; Wheeler, F.J.; Bradshaw, K.M.; Wessol, D.E.; Harker, Y.D.; Nigg, D.W.; Randolph, P.D.; Bauer, W.F.; Gavin, P.R.; Richards, T.L.

1992-01-01

The Power Burst Facility/Boron Neutron Capture Therapy (PBF/BNCT) Program has been funded since 1988 to evaluate brain tumor treatment using Na 2 B 12 H 11 SH (borocaptate sodium or BSH) and epithermal neutrons. The PBF/BNCT Program pursues this goal as a comprehensive, multidisciplinary, multiorganizational endeavor applying modern program management techniques. The initial focus was to: (1) establish a representative large animal model and (2) develop the generic analytical and measurement capabilities require to control treatment repeatability and determine critical treatment parameters independent of tumor type and body location. This paper will identify the PBF/BNCT Program elements and summarize the status of some of the developed capabilities

Boron uptake measurements in a rat model for Boron Neutron Capture Therapy of lung tumours

Energy Technology Data Exchange (ETDEWEB)

Bortolussi, S., E-mail: silva.bortolussi@pv.infn.i [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Ballarini, F. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Gadan, M.A. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Protti, N.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy); Clerici, A.; Ferrari, C.; Cansolino, L.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, via Ferrata 27100 Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, via Ferrata 27100 Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, via Bassi 6, 27100 Pavia (Italy); National Institute of Nuclear Physics (INFN), Section of Pavia, via Bassi 6, 27100 Pavia (Italy)

2011-02-15

Lung carcinoma is the leading cause of cancer mortality in the Western countries. Despite the introduction over the last few years of new therapeutic agents, survival from lung cancer has shown no discernible improvement in the last 20 years. For these reasons any efforts to find and validate new effective therapeutic procedures for lung cancer are very timely. The selective boron uptake in the tumour with respect to healthy tissues makes Boron Neutron Capture Therapy a potentially advantageous option in the treatment of tumours that affect whole vital organs, and that are surgically inoperable. To study the possibility of applying BNCT to the treatment of diffuse pulmonary tumours, an animal model for boron uptake measurements in lung metastases was developed. Both healthy and tumour-bearing rats were infused with Boronophenylalanine (BPA) and sacrificed at different time intervals after drug administration. The lungs were extracted, and prepared for boron analysis by neutron autoradiography and {alpha}-spectroscopy. The boron concentrations in tumour and normal lung were plotted as a function of the time elapsed after BPA administration. The concentration in tumour is almost constant within the error bars for all the time intervals of the experiment (1-8 h), while the curve in normal lung decreases after 4 h from BPA infusion. At 4 h, the ratio of boron concentration in tumour to boron concentration in healthy lung is higher than 3, and it stays above this level up to 8 h. Also the images of boron distribution in the samples, obtained by neutron autoradiography, show a selective absorption in the metastases.

Research related to boron neutron capture therapy at The Ohio State University

International Nuclear Information System (INIS)

Barth, R.F.; Soloway, A.H.; Alam, F.

1986-01-01

Research in the area of boron neutron capture therapy (BNCT) at The Ohio State University is a highly multidisciplinary effort involving approximately twenty investigators in nine different departments. Major areas of interest include: (1) Boronation of monoclonal antibodies directed against tumor-associated antigens for the delivery of 10 B; (2) Synthesis of 10 B-containing derivatives of promazines and porphyrins that possess tumor-localizing properties; (3) Development of a rat model for the treatment of glioblastoma by BNCT; (4) Quantitation and microdistribution of 10 B in tissues by means of a solid state nuclear track detector. The ultimate goal of this research is to carry out the extensive preclinical studies that are required to bring BNCT to the point of a clinical trial. 13 references

Optimal Neutron Source and Beam Shaping Assembly for Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Vujic, J.; Greenspan, E.; Kastenber, W.E.; Karni, Y.; Regev, D.; Verbeke, J.M.; Leung, K.N.; Chivers, D.; Guess, S.; Kim, L.; Waldron, W.; Zhu, Y.

2003-01-01

There were three objectives to this project: (1) The development of the 2-D Swan code for the optimization of the nuclear design of facilities for medical applications of radiation, radiation shields, blankets of accelerator-driven systems, fusion facilities, etc. (2) Identification of the maximum beam quality that can be obtained for Boron Neutron Capture Therapy (BNCT) from different reactor-, and accelerator-based neutron sources. The optimal beam-shaping assembly (BSA) design for each neutron source was also to e obtained. (3) Feasibility assessment of a new neutron source for NCT and other medical and industrial applications. This source consists of a state-of-the-art proton or deuteron accelerator driving and inherently safe, proliferation resistant, small subcritical fission assembly

Effective chemotherapy of acute myelocytic leukemia occurring after alkylating agent or radiation therapy for prior malignancy

International Nuclear Information System (INIS)

Vaughan, W.P.; Karp, J.E.; Burke, P.J.

1983-01-01

Eleven consecutive patients with acute myelocytic leukemia occurring as a second malignancy were treated with high-dose, timed, sequential chemotherapy. Eight of the patients were felt to have ''secondary'' acute leukemia because they had received an alkylating agent or radiation therapy. The other three patients were considered controls. Despite a median age of 65, four of the eight secondary leukemia patients achieved complete remission with this regimen. One of the three control patients also achieved complete remission. This remission rate and duration are comparable to what was achieved with this treatment of ''primary'' acute myelocytic leukemia during the same period of time. These results suggest that patients with leukemia occurring after an alkylating agent or radiation therapy are not at especially high risk if treated aggressively

A critical assessment of boron target compounds for boron neutron capture therapy.

Science.gov (United States)

Hawthorne, M Frederick; Lee, Mark W

2003-01-01

Boron neutron capture therapy (BNCT) has undergone dramatic developments since its inception by Locher in 1936 and the development of nuclear energy during World War II. The ensuing Cold War spawned the entirely new field of polyhedral borane chemistry, rapid advances in nuclear reactor technology and a corresponding increase in the number to reactors potentially available for BNCT. This effort has been largely oriented toward the eradication of glioblastoma multiforme (GBM) and melanoma with reduced interest in other types of malignancies. The design and synthesis of boron-10 target compounds needed for BNCT was not channeled to those types of compounds specifically required for GBM or melanoma. Consequently, a number of potentially useful boron agents are known which have not been biologically evaluated beyond a cursory examination and only three boron-10 enriched target species are approved for human use following their Investigational New Drug classification by the US Food and Drug Administration; BSH, BPA and GB-10. All ongoing clinical trials with GBM and melanoma are necessarily conducted with one of these three species and most often with BPA. The further development of BNCT is presently stalled by the absence of strong support for advanced compound evaluation and compound discovery driven by recent advances in biology and chemistry. A rigorous demonstration of BNCT efficacy surpassing that of currently available protocols has yet to be achieved. This article discusses the past history of compound development, contemporary problems such as compound classification and those problems which impede future advances. The latter include means for biological evaluation of new (and existing) boron target candidates at all stages of their development and the large-scale synthesis of boron target species for clinical trials and beyond. The future of BNCT is bright if latitude is given to the choice of clinical disease to be treated and if a recognized study

Effects of boron neutron capture therapy using borocaptate sodium in combination with a tumor-selective vasoactive agent in mice

International Nuclear Information System (INIS)

Ono, Koji; Masunaga, Shin-ichiro; Kinashi, Yuko; Takagaki, Masao; Akaboshi, Mitsuhiko; Suzuki, Minoru; Baba, Hideo.

1998-01-01

Boron neutron capture therapy (BNCT) destroys tumor cells by means of α particles and recoil protons emitted by 10 B(n,α) 7 Li reaction. For BNCT to be effective, the tumor/normal tissue concentration ratio of 10 B must be larger than 1.0, because neutron distribution is not selective. We examined the combination of 10 B-enriched borocaptate sodium (BSH) with flavone acetic acid (FAA) as a model compound which causes vascular collapse in squamous cell carcinoma in mice (SCCVII tumors) and would increase the tumor/normal tissue concentration ratio of 10 B. FAA (200 mg/kg, i.p.) was injected, and 5 min later BSH (75 mg/kg, i.v.) was administered, followed 15 to 180 min later by irradiation with thermal neutrons. The 10 B concentrations were measured by prompt gamma ray spectrometry. Without FAA, tumor 10 B concentrations were less than or equal to normal tissue concentrations at all time intervals, except that the concentrations were 1.7- to 2.7-fold greater in tumor than muscle at 15 and 180 min after injection of BSH. With FAA, 10 B concentrations 2.1- to 6.9-fold greater in tumor than in muscle were achieved at all intervals tested. For blood and skin, significant differential accumulations were found in tumors at 120 and 180 min. Tumor/liver ratios were less than 1 at all times. Cell survival was determined by in vivo/in vitro colony assay, and increasing radiosensitization correlated with increasing tumor 10 B concentrations, whether or not they were achieved with FAA. Tumor control rates, determined at 180 days after BNCT, similarly appeared to depend only on 10 B levels at the time of irradiation. Because 10 B levels correlate with the radiation response of tissues, a therapeutic gain would be expected whenever the tumor levels exceed normal tissue levels, such as in tumors located in muscle irradiated at 15-180 min after FAA+BSH, or in those in skin irradiated at 120 and 180 min. (author)

Analysis of MCNP simulated gamma spectra of CdTe detectors for boron neutron capture therapy.

Science.gov (United States)

Winkler, Alexander; Koivunoro, Hanna; Savolainen, Sauli

2017-06-01

The next step in the boron neutron capture therapy (BNCT) is the real time imaging of the boron concentration in healthy and tumor tissue. Monte Carlo simulations are employed to predict the detector response required to realize single-photon emission computed tomography in BNCT, but have failed to correctly resemble measured data for cadmium telluride detectors. In this study we have tested the gamma production cross-section data tables of commonly used libraries in the Monte Carlo code MCNP in comparison to measurements. The cross section data table TENDL-2008-ACE is reproducing measured data best, whilst the commonly used ENDL92 and other studied libraries do not include correct tables for the gamma production from the cadmium neutron capture reaction that is occurring inside the detector. Furthermore, we have discussed the size of the annihilation peaks of spectra obtained by cadmium telluride and germanium detectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy (BNCT) for high-grade gliomas of the brain: a cautionary note

International Nuclear Information System (INIS)

Laramore, George E.; Spence, Alexander M.

1996-01-01

Purpose/Objective: Boron neutron capture therapy (BNCT) is a method of treating high-grade gliomas of the brain that involves incorporating 10 B into the tumor using appropriate pharmacological agents and then irradiating the tumor with thermal or epithermal neutron beams. To date, over 120 patients have been treated in this manner by Japanese investigators using a thermal neutron beam from a nuclear reactor. Favorable reports on outcome have motivated considerable current research in BNCT. The purpose of this study is to provide an independent analysis of the Japanese data by identifying the subset of patients from the United States who received this treatment in Japan and comparing their outcomes relative to a matched cohort who received conventional therapy in various Radiation Therapy Oncology Group (RTOG) studies. Methods and Materials: The principal referral sources of patients to Japan for BNCT were identified and the names of patients sent for treatment obtained. The treating physicians in Japan were also contacted to see if additional patients from the United States had been treated. Either the patients or their next of kin were contacted, and permission was obtained to retrieve medical records including tumor pathology for central review. Prognostic variables according to an analysis of the RTOG brain tumor database by Curran et al. were determined from these records and used to construct a matched cohort of patients treated conventionally. Results: A total of 14 patients were identified who had traveled to Japan for BNCT treatment between July, 1987 and June, 1994. In the case of one patient (deceased), it was not possible to contact the next of kin. Material was obtained on the other 13 patients and review of the pathology indicated that 1 patient had a central nervous system lymphoma rather than a high-grade glioma. Survival data was analyzed for the other 12 patients on an actuarial basis, and this showed no difference compared to survival data for a

Targeted therapies for diarrhea-predominant irritable bowel syndrome

Science.gov (United States)

Olden, Kevin W

2012-01-01

Irritable bowel syndrome (IBS) causes gastrointestinal symptoms such as abdominal pain, bloating, and bowel pattern abnormalities, which compromise patients’ daily functioning. Common therapies address one or two IBS symptoms, while others offer wider symptom control, presumably by targeting pathophysiologic mechanisms of IBS. The aim of this targeted literature review was to capture clinical trial reports of agents receiving the highest recommendation (Grade 1) for treatment of IBS from the 2009 American College of Gastroenterology IBS Task Force, with an emphasis on diarrhea-predominant IBS. Literature searches in PubMed captured articles detailing randomized placebo-controlled trials in IBS/diarrhea-predominant IBS for agents receiving Grade I (strong) 2009 American College of Gastroenterology IBS Task Force recommendations: tricyclic antidepressants, nonabsorbable antibiotics, and the 5-HT3 receptor antagonist alosetron. Studies specific for constipation-predominant IBS were excluded. Tricyclic antidepressants appear to improve global IBS symptoms but have variable effects on abdominal pain and uncertain tolerability; effects on stool consistency, frequency, and urgency were not adequately assessed. Nonabsorbable antibiotics show positive effects on global symptoms, abdominal pain, bloating, and stool consistency but may be most efficacious in patients with altered intestinal microbiota. Alosetron improves global symptoms and abdominal pain and normalizes bowel irregularities, including stool frequency, consistency, and fecal urgency. Both the nonabsorbable antibiotic rifaximin and the 5-HT3 receptor antagonist alosetron improve quality of life. Targeted therapies provide more complete relief of IBS symptoms than conventional agents. Familiarization with the quantity and quality of evidence of effectiveness can facilitate more individualized treatment plans for patients with this heterogeneous disorder. PMID:22754282

Biological models in vivo for boron neutronic capture studies as tumors therapy

International Nuclear Information System (INIS)

Kreimann, Erica L.; Dagrosa, Maria A.; Schwint, Amanda E.; Itoiz, Maria E.; Pisarev, Mario A.; Farias, Silvia S.; Garavaglia, Ricardo N.; Batistoni, Daniel A.

1999-01-01

The use of experimental models for Boron Neutronic Capture studies as Tumors Therapy have as two main objectives: 1) To contribute to the basic knowledge of the biological mechanisms involved to increase the method therapeutical advantage, and 2) To explore the possible application of this therapeutic method to other pathologies. In this frame it was studied the carcinogenesis model of hamster cheek pouch, a type of human buccal cancer. Biodistribution studies of boron compound were performed in tumor, blood and in different precancerous and normal tissues as well as BNCT studies. Results validated this method for BNCT studies and show the capacity of the oral mucosa tumors of selectively concentrate the boron compound, showing a deleterious clear effect on the tumor after 24 hours with BNCT treatment. (author)

Boron neutron capture therapy induces cell cycle arrest and DNA fragmentation in murine melanoma cells

Energy Technology Data Exchange (ETDEWEB)

Faiao-Flores, F. [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)] [Faculty of Medicine, University of Sao Paulo, 455 Doutor Arnaldo Avenue, Sao Paulo (Brazil); Coelho, P.R.P. [Institute for Nuclear and Energy Research, 2242 Lineu Prestes Avenue, Sao Paulo (Brazil); Arruda-Neto, J. [Physics Institute, University of Sao Paulo, 187 Matao Street, Sao Paulo (Brazil)] [FESP, Sao Paulo Engineering School, 5520 Nove de Julho Avenue, Sao Paulo (Brazil); Maria, Durvanei A., E-mail: durvaneiaugusto@yahoo.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

2011-12-15

The melanoma is a highly lethal skin tumor, with a high incidence. Boron Neutron Capture Therapy (BNCT) is a radiotherapy which combines Boron with thermal neutrons, constituting a binary system. B16F10 melanoma and L929 fibroblasts were treated with Boronophenylalanine and irradiated with thermal neutron flux. The electric potential of mitochondrial membrane, cyclin D1 and caspase-3 markers were analyzed. BNCT induced a cell death increase and cyclin D1 amount decreased only in B16F10 melanoma. Besides, there was not caspase-3 phosphorylation.

Possible application of boron neutron capture therapy to canine osteosarcoma

International Nuclear Information System (INIS)

Takeuchi, Akira

1985-01-01

Possibility for successful treatment of canine osteosarcoma by boron neutron capture therapy (BNCT) was demonstrated based upon an uptake study of the boron compound and an experimental treatment by BNCT. In the up take study following intravenous administration of Na 2 B 12 H 11 SH, satisfactorily higher boron concentration with some variation between tumors is likely to be obtained 12 hours after the administration, together with significantly lower boron levels in blood and bone. Based upon these results, osteosarcoma of a mongrel dog was successfully treated by BNCT. The tumor received approximately 3800 rads with single neutron irradiation (approximately 1.4 x 10 13 n./cm 2 ) about 12 hours after intravenous infusion of Na 2 B 12 H 11 SH of 96 % enriched 10 B in the ratio of 50 mg 10 B/kg. Clinical and radiographical improvements were remarkable and no neoplastic cell was found in any part of the original neoplastic lesion and its surrounding tissue at the time of autopsy after 30 days. (author)

Irradiation system for neutron capture therapy using the small accelerator

International Nuclear Information System (INIS)

Kobayashi, Tooru; Hoshi, Masaharu

2002-01-01

Neutron capture therapy (NCT) is to kill tumor cells that previously incorporated the stable isotope which generates heavy charged particles with a short range and a high linear energy transfer (LET) on neutron irradiation. Boron-10 is ordinarily used as such an isotope. The tumor tissue is neutron-irradiated at craniotomy after preceding craniotomy for tumor extraction: therefore two surgeries are required for the present NCT in Japan. The reactions 10 B(n, αγ) 7 Li and 7 Li (p, n) 7 Be are thought preferential for patients and doctors if a convenient small accelerator, not the reactor used at present, is available in the hospital because only one craniotomy is sufficient. Authors' examinations of the system for NCT using the small accelerator involve irradiation conditions, desirable energy spectrum of neutron, characterization of thermal and epi-thermal neutrons, social, practical and technical comparison of the reactor and accelerator, and usefulness of the reaction 7 Li (p, n) 7 Be. The system devoted to the NCT is awaited in future. (K.H.)

Application of adjoint Monte Carlo to accelerate simulations of mono-directional beams in treatment planning for Boron Neutron Capture Therapy

NARCIS (Netherlands)

Nievaart, V.A.; Legrady, D.; Moss, R.L.; Kloosterman, J.L.; Van der Hagen, T.H.; Van Dam, H.

2007-01-01

This paper deals with the application of the adjoint transport theory in order to optimize Monte Carlo based radiotherapy treatment planning. The technique is applied to Boron Neutron Capture Therapy where most often mixed beams of neutrons and gammas are involved. In normal forward Monte Carlo

System and process for capture of H.sub.2S from gaseous process streams and process for regeneration of the capture agent

Science.gov (United States)

Heldenbrant, David J; Koech, Phillip K; Rainbolt, James E; Bearden, Mark D; Zheng, Feng

2014-02-18

A system and process are disclosed for selective removal and recovery of H.sub.2S from a gaseous volume, e.g., from natural gas. Anhydrous organic, sorbents chemically capture H.sub.2S gas to form hydrosulfide salts. Regeneration of the capture solvent involves addition of an anti-solvent that releases the captured H.sub.2S gas from the capture sorbent. The capture sorbent and anti-solvent are reactivated for reuse, e.g., by simple distillation.

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head and Neck Cancer

International Nuclear Information System (INIS)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna; Saarilahti, Kauko; Atula, Timo; Collan, Juhani; Salli, Eero; Kortesniemi, Mika; Uusi-Simola, Jouni; Maekitie, Antti; Seppaenen, Marko; Minn, Heikki; Kotiluoto, Petri; Auterinen, Iiro; Savolainen, Sauli; Kouri, Mauri; Joensuu, Heikki

2007-01-01

Purpose: Head and neck carcinomas that recur locally after conventional irradiation pose a difficult therapeutic problem. We evaluated safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of such cancers. Methods and Materials: Twelve patients with inoperable, recurred, locally advanced (rT3, rT4, or rN2) head and neck cancer were treated with BNCT in a prospective, single-center Phase I-II study. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 56-74 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria and adverse effects using the National Cancer Institute common toxicity grading v3.0. Intravenously administered boronophenylalanine-fructose (BPA-F, 400 mg/kg) was used as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Ten patients received BNCT twice; 2 were treated once. Ten (83%) patients responded to BNCT, and 2 (17%) had tumor growth stabilization for 5.5 and 7.6 months. The median duration of response was 12.1 months; six responses were ongoing at the time of analysis or death (range, 4.9-19.2 months). Four (33%) patients were alive without recurrence with a median follow-up of 14.0 months (range, 12.8-19.2 months). The most common acute adverse effects were mucositis, fatigue, and local pain; 2 patients had a severe (Grade 3) late adverse effect (xerostomia, 1; dysphagia, 1). Conclusions: Boron neutron capture therapy is effective and safe in the treatment of inoperable, locally advanced head and neck carcinomas that recur at previously irradiated sites

A shielding design for an accelerator-based neutron source for boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Hawk, A.E.; Blue, T.E. E-mail: blue.1@osu.edu; Woollard, J.E

2004-11-01

Research in boron neutron capture therapy (BNCT) at The Ohio State University Nuclear Engineering Department has been primarily focused on delivering a high quality neutron field for use in BNCT using an accelerator-based neutron source (ABNS). An ABNS for BNCT is composed of a proton accelerator, a high-energy beam transport system, a {sup 7}Li target, a target heat removal system (HRS), a moderator assembly, and a treatment room. The intent of this paper is to demonstrate the advantages of a shielded moderator assembly design, in terms of material requirements necessary to adequately protect radiation personnel located outside a treatment room for BNCT, over an unshielded moderator assembly design.

Data Provenance for Agent-Based Models in a Distributed Memory

Directory of Open Access Journals (Sweden)

Delmar B. Davis

2018-04-01

Full Text Available Agent-Based Models (ABMs assist with studying emergent collective behavior of individual entities in social, biological, economic, network, and physical systems. Data provenance can support ABM by explaining individual agent behavior. However, there is no provenance support for ABMs in a distributed setting. The Multi-Agent Spatial Simulation (MASS library provides a framework for simulating ABMs at fine granularity, where agents and spatial data are shared application resources in a distributed memory. We introduce a novel approach to capture ABM provenance in a distributed memory, called ProvMASS. We evaluate our technique with traditional data provenance queries and performance measures. Our results indicate that a configurable approach can capture provenance that explains coordination of distributed shared resources, simulation logic, and agent behavior while limiting performance overhead. We also show the ability to support practical analyses (e.g., agent tracking and storage requirements for different capture configurations.

Clinical Evaluation of applying a hydrophobic and a hydrophilic bonding agent on the retention and durability of fissure sealant therapy

Directory of Open Access Journals (Sweden)

Mostafa GHandi

2016-03-01

Full Text Available Background and Aims: As in fissure sealant therapy the tooth surface is mostly enamel, the use of an enamel bonding agent (hydrophobic bonding agent may be more cost effective than that of newer generations of bonding (hydrophilic bonding agents. The aim of this study was to compare the retention and durability of fissure sealant therapy when applying an enamel bonding agent, a dentin bonding agent and no bonding agent during 4 years. Materials and Methods: This study was done on the first permanent molars of the upper and lower jaws of 24 students of the first grade of a primary school (6-7 years old. On 36 teeth, a dentin bonding agent (Excite was applied under the fissure sealant and on 36 teeth an enamel bonding agent (Margin bond was applied under the fissure sealant. Then, 24 teeth were selected from these two groups and were compared with a group (including 24 teeth with no bonding agent under the fissure sealant (as control group. All the fissures of the teeth were evaluated annually for 4 years to find out the presence or absence of fissure sealant substance. Data were analyzed using Wilcoxon test. Results: From the statistical analysis, there was no significant difference in retention and durability of the fissure sealant substance comparing the group with dentin bonding agent (Excite and the group with enamel bonding agent (Margin bond. Also, using a bonding agent made no significant difference (P>0.05. Conclusion: According to the results of this study, using a bonding agent made no improvement in the retention and durability of fissure sealant substance.

The 3D tomographic image reconstruction software for prompt-gamma measurement of the boron neutron capture therapy

International Nuclear Information System (INIS)

Morozov, Boris; Auterinen, Iiro; Kotiluoto, Petri; Kortesniemi, Mika

2006-01-01

A tomographic imaging system based on the spatial distribution measurement of the neutron capture reaction during Boron Neutron Capture Therapy (BNCT) would be very useful for clinical purpose. Using gamma-detectors in a 2D-panel, boron neutron capture and hydrogen neutron capture gamma-rays emitted by the neutron irradiated region can be detected, and an image of the neutron capture events can be reconstructed. A 3D reconstruction software package has been written to support the development of a 3D prompt-gamma tomographic system. The package consists of three independent modules: phantom generation, reconstruction and evaluation modules. The reconstruction modules are based on algebraic approach of the iterative reconstruction algorithm (ART), and on the maximum likelihood estimation method (ML-EM). In addition to that, two subsets of the ART, the simultaneous iterative reconstruction technique (SIRT) and the component averaging algorithms (CAV) have been included to the package employing parallel codes for multiprocessor architecture. All implemented algorithms use two different field functions for the reconstruction of the region. One is traditional voxel function, another is, so called, blob function, smooth spherically symmetric generalized Kaiser-Bessel function. The generation module provides the phantom and projections with background by tracing the prompt gamma-rays for a given scanner geometry. The evaluation module makes statistical comparisons between the generated and reconstructed images, and provides figure-of-merit (FOM) values for the applied reconstruction algorithms. The package has been written in C language and tested under Linux and Windows platforms. The simple graphical user interface (GUI) is used for command execution and visualization purposed. (author)

Security Infrastructure and Applicationsfor Mobile Agents

OpenAIRE

Shibli, Awais

2010-01-01

Research areas of this dissertation are security for mobile agents, for applications based on mobile agents, and for distributed network environments in which mobile agents execute. Mobile agents paradigm has captured researchers’ and industry’s interests long time ago because of its innovative capabilities and attractive applications. The ability of mobile agents to autonomously migrate from host to host, transferring their code and internal state, enables them to accomplish tasks in network...

Boron neutron capture therapy for malignant brain tumor in Japan

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Yoshinobu [National Kagawa Children`s Hospital, Takamatsu, Kagawa (Japan)

1998-03-01

Since 1968, we have treated 149 patients and performed boron-neutron capture therapy (BNCT) on 164 occasions using 5 reactors in Japan. There were 64 patients with glioblastoma, 39 patients with anaplastic astrocytoma and 17 patients with low grade astrocytoma (grade 1 or 2). There were 30 patients with other types of tumor. The overall response rate in the glioma patients was 64%. Seven patients (12%) of glioblastoma, 22 patients (56%) of anaplastic astrocytoma and 8 patients (62%) of low grade astrocytoma lived more than 2 years Median survival time of glioblastoma was 640 days. Median survival times of patients with anaplastic astrocytoma was 1811 days, and 1669 days in low grade astrocytoma. Six patients (5 glioblastoma and one anaplastic astrocytoma) died within 90 days after BNCT. Six patients lived more than 10 years. Histological grading, age of the patients, neutron fluence at the target point and target depth or size of the tumor were proved to be important factors. BNCT is an effective treatment for malignant brain tumors. We are now became able to radiate the tumor more correctly with a high enough dose of neutron beam even if we use thermal neutron beam. (author)

Electrostatic design and beam transport for a folded tandem electrostatic quadrupole accelerator facility for accelerator-based boron neutron capture therapy

International Nuclear Information System (INIS)

Thatar Vento, V.; Bergueiro, J.; Cartelli, D.; Valda, A.A.; Kreiner, A.J.

2011-01-01

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam.

Hyper-thermal neutron irradiation field for neutron capture therapy

International Nuclear Information System (INIS)

Sakurai, Yoshinori; Kobayashi, Tooru; Kanda, Keiji

1994-01-01

The utilization of hyper-thermal neutrons, which have an energy spectrum of a Maxwell distribution higher than the room temperature of 300 K, has been studied in order to improve the thermal neutron flux distribution in a living body for a deep-seated tumor in neutron capture therapy (NCT). Simulation calculations using MCNP-V3 were carried out in order to investigate the characteristics of the hyper-thermal neutron irradiation field. From the results of simulation calculations, the following were confirmed: (i) The irradiation field of the hyper-thermal neutrons is feasible by using some scattering materials with high temperature, such as Be, BeO, C, SiC and ZrH 1.7 . Especially, ZrH 1.7 is thought to be the best material because of good characteristics of up-scattering for thermal neutrons. (ii) The ZrH 1.7 of 1200 K yields the hyper-thermal neutrons of a Maxwell-like distribution at about 2000 K and the treatable depth is about 1.5 cm larger comparing with the irradiation of the thermal neutrons of 300 K. (iii) The contamination by the secondary gamma-rays from the scattering materials can be sufficiently eliminated to the tolerance level for NCT through the bismuth layer, without the larger change of the energy spectrum of hyper-thermal neutrons. ((orig.))

Current status of accelerator-based boron neutron capture therapy

International Nuclear Information System (INIS)

Kreiner, A. J.; Bergueiro, J.; Di Paolo, H.; Castell, W.; Vento, V. Thatar; Cartelli, D.; Kesque, J.M.; Valda, A.A.; Ilardo, J.C.; Baldo, M.; Erhardt, J.; Debray, M.E.; Somacal, H.R.; Estrada, L.; Sandin, J.C. Suarez; Igarzabal, M.; Huck, H.; Padulo, J.; Minsky, D.M.

2011-01-01

The direct use of proton and heavy ion beams for radiotherapy is a well established cancer treatment modality, which is becoming increasingly widespread due to its clear advantages over conventional photon-based treatments. This strategy is suitable when the tumor is spatially well localized. Also the use of neutrons has a long tradition. Here Boron Neutron Capture Therapy (BNCT) stands out, though on a much smaller scale, being a second-generation promising alternative for tumors which are diffuse and infiltrating. On this sector, so far only nuclear reactors have been used as neutron sources. In this paper we describe the current situation worldwide as far as the use of accelerator-based neutron sources for BNCT is concerned (so-called Accelerator-Based (AB)-BNCT). In particular we discuss the present status of an ongoing project to develop a folded Tandem-ElectroStatic-Quadrupole (TESQ) accelerator at the Atomic Energy Commission of Argentina. The project goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the 7 Li(p,n) 7 Be reaction. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams to perform BNCT for deep-seated tumors in less than an hour. (author)

Application of generalized perturbation theory to sensitivity analysis in boron neutron capture therapy

International Nuclear Information System (INIS)

Garcia, Vanessa S.; Silva, Fernando C.; Silva, Ademir X.; Alvarez, Gustavo B.

2011-01-01

Boron neutron capture therapy - BNCT - is a binary cancer treatment used in brain tumors. The tumor is loaded with a boron compound and subsequently irradiated by thermal neutrons. The therapy is based on the 10 B (n, α) 7 Li nuclear reaction, which emits two types of high-energy particles, α particle and the 7 Li nuclei. The total kinetic energy released in this nuclear reaction, when deposited in the tumor region, destroys the cancer cells. Since the success of the BNCT is linked to the different selectivity between the tumor and healthy tissue, it is necessary to carry out a sensitivity analysis to determinate the boron concentration. Computational simulations are very important in this context because they help in the treatment planning by calculating the lowest effective absorbed dose rate to reduce the damage to healthy tissue. The objective of this paper is to present a deterministic method based on generalized perturbation theory (GPT) to perform sensitivity analysis with respect to the 10 B concentration and to estimate the absorbed dose rate by patients undergoing this therapy. The advantage of the method is a significant reduction in computational time required to perform these calculations. To simulate the neutron flux in all brain regions, the method relies on a two-dimensional neutron transport equation whose spatial, angular and energy variables are discretized by the diamond difference method, the discrete ordinate method and multigroup formulation, respectively. The results obtained through GPT are consistent with those obtained using other methods, demonstrating the efficacy of the proposed method. (author)

Application of generalized perturbation theory to sensitivity analysis in boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Garcia, Vanessa S. [Universidade Federal Fluminense (EEIMVR/UFF-RJ), Volta Redonda, RJ (Brazil). Escola de Engenharia Industrial e Metalurgica. Programa de Pos-Graduacao em Modelagem Computacional em Ciencia e Tecnologia; Silva, Fernando C.; Silva, Ademir X., E-mail: fernando@con.ufrj.b, E-mail: ademir@con.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEN/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Alvarez, Gustavo B. [Universidade Federal Fluminense (EEIMVR/UFF-RJ), Volta Redonda, RJ (Brazil). Escola de Engenharia Industrial e Metalurgica. Dept. de Ciencias Exatas

2011-07-01

Boron neutron capture therapy - BNCT - is a binary cancer treatment used in brain tumors. The tumor is loaded with a boron compound and subsequently irradiated by thermal neutrons. The therapy is based on the {sup 10}B (n, {alpha}) {sup 7}Li nuclear reaction, which emits two types of high-energy particles, {alpha} particle and the {sup 7}Li nuclei. The total kinetic energy released in this nuclear reaction, when deposited in the tumor region, destroys the cancer cells. Since the success of the BNCT is linked to the different selectivity between the tumor and healthy tissue, it is necessary to carry out a sensitivity analysis to determinate the boron concentration. Computational simulations are very important in this context because they help in the treatment planning by calculating the lowest effective absorbed dose rate to reduce the damage to healthy tissue. The objective of this paper is to present a deterministic method based on generalized perturbation theory (GPT) to perform sensitivity analysis with respect to the {sup 10}B concentration and to estimate the absorbed dose rate by patients undergoing this therapy. The advantage of the method is a significant reduction in computational time required to perform these calculations. To simulate the neutron flux in all brain regions, the method relies on a two-dimensional neutron transport equation whose spatial, angular and energy variables are discretized by the diamond difference method, the discrete ordinate method and multigroup formulation, respectively. The results obtained through GPT are consistent with those obtained using other methods, demonstrating the efficacy of the proposed method. (author)

Characteristics of neutron irradiation facility and dose estimation method for neutron capture therapy at Kyoto University research reactor institute

International Nuclear Information System (INIS)

Kobayashi, T.; Sakurai, Y.; Kanda, K.

2001-01-01

The neutron irradiation characteristics of the Heavy Water Neutron Irradiation Facility (HWNIF) at the Kyoto University Research Reactor Institute (KIJRRI) for boron neutron capture therapy (BNCT), is described. The present method of dose measurement and its evaluation at the KURRI, is explained. Especially, the special feature and noticeable matters were expounded for the BNCT with craniotomy, which has been applied at present only in Japan. (author)

Boron neutron capture therapy: A guide to the understanding of the pathogenesis of late radiation damage to the rat spinal cord

International Nuclear Information System (INIS)

Morris, G.M.; Whitehouse, E.M.; Hopewell, J.W.; Coderre, J.A.; Micca, P.

1994-01-01

Before the commencement of new boron neutron capture therapy (BNCT) clinical trials in Europe and North America, detailed information on normal tissue tolerance is required. In this study, the pathologic effects of BNCT on the central nervous system (CNS) have been investigated using a rat spinal cord model. The neutron capture agent used was 10 B-enriched sodium mercaptoundecahydro-closo-dodecaborate (BSH), at a dosage of 100 mg/kg body weight. Rats were irradiated on the thermal beam at the Brookhaven Medical Research Reactor. The large spine of vertebra T 2 was used as the lower marker of the irradiation field. Rats were irradiated with thermal neutrons alone to a maximum physical absorbed dose of 11.4 Gy, or with thermal neutrons in combination with BSH, to maximum absorbed physical doses of 5.7 Gy to the CNS parenchyma and 33.7 Gy to the blood in the vasculature of the spinal cord. An additional group of rats was irradiated with 250 kVp X-rays to a single dose of 35 Gy. Spinal cord pathology was examined between 5 and 12 months after irradiation. The physical dose of radiation delivered to the CNS parenchyma, using thermal neutron irradiation in the presence of BSH, was a factor of two to three lower than that delivered to the vascular endothelium, and could not account for the level of damage observed in the parenchyma. The histopathological observations of the present study support the hypothesis that the blood vessels, and the endothelial cells in particular, are the critical target population responsible for the lesions seen in the spinal cord after BNCT type irradiation and by inference, after more conventional irradiation modalities such as photons or fast neutrons. 30 refs., 6 figs., 1 tab

Impact of Therapy Sequence with Alkylating Agents and MGMT Status in Patients with Advanced Neuroendocrine Tumors.

Science.gov (United States)

Krug, Sebastian; Boch, Michael; Rexin, Peter; Gress, Thomas M; Michl, Patrick; Rinke, Anja

2017-05-01

Alkylating chemotherapeutics with either a streptozotocin-(STZ) or temozolomide-(TEM) backbone are routinely used in patients with progressive and unresectable pancreatic neuroendocrine tumors (PNET). In addition, dacarbazine (DTIC) was described as an alternative alkylating therapy option for PNETs. The optimal treatment sequence with alkylating compounds and a potential use of O6-methylguanine-DNA methyltransferase (MGMT) level as predictive biomarker have not yet been sufficiently elucidated. The aim of our study was the evaluation of therapy sequence with either STZ-based treatment followed by DTIC (group A) or the inverse schedule with upfront DTIC (group B) and to correlate MGMT status with clinicopathological characteristics and response to therapy. We retrospectively analyzed 28 patients with neuroendocrine tumors (NET) who were treated with STZ-based therapy and DTIC. Additionally, in a second group MGMT immunohistochemistry was performed from primary and metastatic tumor sites. For statistical evaluation Kaplan-Meier analysis, Cox regression methods and Fisher's exact test were used. There was no difference of objective response and disease control between either STZ-based therapy followed by DTIC treatment (group A) after progression or the reverse sequence (group B). Median time to progression (TTP) was estimated to be 21 months in both arms. First-line STZ-based chemotherapy was not superior to first-line DTIC treatment (16 vs. 13 months; p=0.8). MGMT status did not correlate with clinicopathological characteristics or response to therapy with these alkylating agents. Upfront chemotherapy with either STZ-based treatment or DTIC monotherapy showed similar efficacy and median TTP rates. In this study, MGMT protein expression assessed by immunohistochemistry did not play an important role as a predictive marker for alkylating agents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Proton linacs for boron neutron capture therapy

International Nuclear Information System (INIS)

Lennox, A.J.

1993-08-01

Recent advances in the ability to deliver boron-containing drugs to brain tumors have generated interest in ∼4 MeV linacs as sources of epithermal neutrons for radiation therapy. In addition, fast neutron therapy facilities have been studying methods to moderate their beams to take advantage of the high cross section for epithermal neutrons on boron-10. This paper describes the technical issues involved in each approach and presents the motivation for undertaking such studies using the Fermilab linac. the problems which must be solved before therapy can begin are outlined. Status of preparatory work and results of preliminary measurements are presented

Twelve-week, prospective, open-label, randomized trial on the effects of an anticholinergic agent or antidiuretic agent as add-on therapy to an alpha-blocker for lower urinary tract symptoms

Directory of Open Access Journals (Sweden)

Shin YS

2014-07-01

Full Text Available Yu Seob Shin,1 Li Tao Zhang,1 Chen Zhao,2 Young Gon Kim,1 Jong Kwan Park1 1Department of Urology, Chonbuk National University Medical School, and Institute for Medical Sciences, Chonbuk National University and Biomedical Research Institute and Clinical Trial Center of Medical Device of Chonbuk National University Hospital, Jeonju, South Korea; 2Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Institute of Andrology, Shanghai, People’s Republic of China Purpose: The effects of an anticholinergic or antidiuretic agent as add-on therapy to an ­alpha-blocker for lower urinary tract symptoms (LUTS according to a voiding diary in 3 days are unknown. We prospectively investigated the efficacy of an anticholinergic or antidiuretic agent as add-on therapy for nocturia in men previously treated with an alpha-blocker for LUTS.Subjects and methods: Patients were randomly subdivided into two groups. All patients had a 4-week washout. Group A had alpha-blocker for 4 weeks, then an alpha-blocker plus an anticholinergic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an antidiuretic agent. Group B had an alpha-blocker for 4 weeks, then an alpha-blocker plus an antidiuretic agent for 4 weeks, and, finally, 4 weeks of an alpha-blocker plus an anticholinergic agent. In both groups, patients were subdivided into nocturnal polyuria, decreased nocturnal bladder capacity (NBC, or nocturia by both causes subgroups. A 3-day voiding diary, total International Prostate Symptom Score (IPSS, IPSS sub-scores, Overactive Bladder Symptom Score, uroflowmetry, and post-void residual urine volume, were assessed at baseline, and at 4, 8, and 12 weeks.Results: A total of 405 patients completed the study. During treatment, the changes from baseline in total IPSS and IPSS sub-scores were significantly decreased at 4 weeks and were maintained for 12 weeks. In the nocturnal polyuria subgroup of Groups A and B

Progress in study of a medical reactor for boron neutron capture therapy

International Nuclear Information System (INIS)

Sasaki, Makoto; Hirota, Jitsuya; Tamao, Shigeo; Kanda, Keiji; Mishima, Yutaka.

1993-01-01

A design study of a medical reactor for Boron Neutron Capture Therapy has made progress. Main specifications of the reactor are as follows; thermal power of 2 MW, water cooling by natural convection, semitight core of hexagonal lattice, UO 2 fuel rod of 9.5 mm diameter and no refueling in the reactor-life. Three horizontal and one vertical neutron beam holes are to be provided for simultaneous treatments by thermal and epithermal neutrons and for further biomedical research. The design objectives for the beam holes are to deliver the therapeutic doses in a modest time (30 to 60 min) with minimal fast neutron and gamma contaminants. The n-γ coupling Sn transport calculations have been carried out using n-21 and γ-9 group cross sections on 2-dim. practical models. The calculated results indicate that the design objectives will be achievable even if the thermal power of the reactor is reduced to 1 MW. (author)

Primary study for boron neutron capture therapy uses the RSG-GAS beam tube facility

International Nuclear Information System (INIS)

Suroso

2000-01-01

The minimum epithermal neutron flux as one of the prerequisite of Boron Neutron Capture Therapy (BNCT) is 1.0 x 10 9 n/(cm 2 s) RSG-GAS have 6 beam tube facilities for neutron source, which is one of the beam tube S-2 has a possibility to utilization for BNCT facility. The totally flux neutron measurement in the front of S-2 beam tube is 1.8 x 10 7 n/(cm 2 s). The neutron flux measurement was less than for BNCT minimum prerequisite. Concerning to the flux neutron production in the reactor, which is reach to 2.5 x 10 14 n/(cm 2 s), there for the S-2 beam tube could be used beside collimator modification

Biodistribution, toxicity and efficacy of a boronated porphyrin for boron neutron capture therapy

International Nuclear Information System (INIS)

Miura, Michiko; Micca, P.; Fairchild, R.; Slatkin, D.; Gabel, D.

1992-01-01

Boron-containing porphyrins may be useful for boron neutron capture therapy (BNCT) in the treatment of brain tumors. Porphyrins have been shown to accumulate in tumor tissue and to be essentially excluded from normal brain. However, problems of toxicity may prevent some boron-containing porphyrins from being considered for BNCT. The authors have synthesized the boronated porphyrin 2,4-bis-vinyl-o-nidocarboranyl-deuteroporphyrin IX (VCDP). Preliminary studies in tumor-bearing mice showed considerable uptake of boron at a total dose of 150 μg/gbw with low mortality. They now report that a total dose to mice of ∼ 275 μg VCDP/gbw administered in multiple intraperitoneal (ip) injections can provide 40-50μg B per gram of tumor with acceptable toxicity. Toxicity experiments and a preliminary trial of BNCT in mice given such doses are also reported

Boron neutron capture therapy as new treatment for clear cell sarcoma: Trial on different animal model

International Nuclear Information System (INIS)

Andoh, Tooru; Fujimoto, Takuya; Sudo, Tamotsu; Suzuki, Minoru; Sakurai, Yoshinori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Takeuchi, Tamotsu; Sonobe, Hiroshi; Epstein, Alan L.; Fukumori, Yoshinobu; Ono, Koji; Ichikawa, Hideki

2014-01-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS. - Highlights: • BNCT with the use of L-BPA was applied for three human clear cell sarcoma (CCS) cell lines. • BNCT trial was performed on a newly established intramuscularly CCS-bearing animal model. • A significant decrease of the tumor-volume was seen by single BNCT with the use of L-BPA. • A multiple BNCT application would be required for controlling the growth of any residual tumors

How should immunomodulators be optimized when used as combination therapy with anti-tumor necrosis factor agents in the management of inflammatory bowel disease?

Science.gov (United States)

Ward, Mark G; Irving, Peter M; Sparrow, Miles P

2015-10-28

In the last 15 years the management of inflammatory bowel disease has evolved greatly, largely through the increased use of immunomodulators and, especially, anti-tumor necrosis factor (anti-TNF) biologic agents. Within this time period, confidence in the use of anti-TNFs has increased, whilst, especially in recent years, the efficacy and safety of thiopurines has been questioned. Yet despite recent concerns regarding the risk: benefit profile of thiopurines, combination therapy with an immunomodulator and an anti-TNF has emerged as the recommended treatment strategy for the majority of patients with moderate-severe disease, especially those who are recently diagnosed. Concurrently, therapeutic drug monitoring has emerged as a means of optimizing the dosage of both immunomodulators and anti-TNFs. However the recommended therapeutic target levels for both drug classes were largely derived from studies of monotherapy with either agent, or studies underpowered to analyze outcomes in combination therapy patients. It has been assumed that these target levels are applicable to patients on combination therapy also, however there are few data to support this. Similarly, the timing and duration of treatment with immunomodulators when used in combination therapy remains unknown. Recent attention, including post hoc analyses of the pivotal registration trials, has focused on the optimization of anti-TNF agents, when used as either monotherapy or combination therapy. This review will instead focus on how best to optimize immunomodulators when used in combination therapy, including an evaluation of recent data addressing unanswered questions regarding the optimal timing, dosage and duration of immunomodulator therapy in combination therapy patients.

The radiation biology of Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Coderre, J.A.

2003-01-01

Boron Neutron Capture Therapy (BNCT) produces a complex mixture of high and low-LET radiations in tissue. Using data on the biological effectiveness of these various dose components, derived primarily in small animals irradiated with thermal neutrons, it has been possible to express clinical BNCT doses in photon-equivalent units. The accuracy of these calculated doses in normal tissue and tumor will be reviewed. Clinical trials are underway at a number of centers. There are differences in the neutron beams at these centers, and differences in the details of the clinical protocols. Ideally, data from all centers using similar boron compounds and treatment protocols should be compared and combined, if appropriate, in a multi-institutional study in order to strengthen statistical analysis. An international dosimetry exchange is underway that will allow the physical doses from the various treatment centers to be quantitatively compared. As a first step towards the comparison of the clinical data, the normal brain tolerance data from the patients treated in the initial Brookhaven National Laboratory and the Harvard/MIT BNCT clinical trials have been compared. The data provide a good estimate of the normal brain tolerance for a somnolence syndrome endpoint, and provide guidance for setting normal brain tolerance limits in ongoing and future clinical trials. Escalation of the dose in BNCT can be accomplished by increasing the amount of the boron compound administered, increasing the duration of the neutron exposure, or both. The dose escalations that have been carried out to date at the various treatment centers will be compared and contrasted. Possible future clinical trials using BNCT in combination with other modalities will be discussed

Boron neutron capture therapy in cancer: past, present and future

Energy Technology Data Exchange (ETDEWEB)

Pisarev, Mario A.; Dagrosa, Maria Alejandra; Juvenal, Guilermo J. [National Atomic Energy Commission, Buenos Aires (Argentina). Div. of Nuclear Biochemistry; University of Buenos Aires (Argentina). School of Medicine. Dept. of Human Biochemistry

2007-07-15

Undifferentiated thyroid cancer (UTC) is a very aggressive tumor with no effective treatment, since it lacks iodine uptake and does not respond to radio or chemotherapy. The prognosis of these patients is bad, due to the rapid growth of the tumor and the early development of metastasis. Boron neutron capture therapy (BNCT) is based on the selective uptake of certain boron non-radioactive compounds by a tumor, and the subsequent irradiation of the area with an appropriate neutron beam. {sup 10}B is then activated to {sup 11}B, which will immediately decay releasing alpha particles and {sup 7}Li, of high linear energy transfer (LET) and limited reach. Clinical trials are being performed in patients with glioblastoma multiform and melanoma. We have explored its possible application to UTC. Our results demonstrated that a cell line of human UTC has a selective uptake of borophenylalanine (BPA) both in vitro and after transplantation to nude mice. Treatment of mice by BNCT led to a complete control of growth and cure of 100% of the animals. Moreover dogs with spontaneous UTC also have a selective uptake of BPA. At the present we are studying the biodistribution of BPA in patients with UTC before its application in humans. (author)

Gadolinia nanofibers as a multimodal bioimaging and potential radiation therapy agent

Science.gov (United States)

Grishin, A. M.; Jalalian, A.; Tsindlekht, M. I.

2015-05-01

Continuous bead-free C-type cubic gadolinium oxide (Gd2O3) nanofibers 20-30 μm long and 40-100 nm in diameter were sintered by sol-gel calcination assisted electrospinning technique. Dipole-dipole interaction of neighboring Gd3+ ions in nanofibers with large length-to-diameter aspect ratio results in some kind of superparamagnetic behavior: fibers are magnetized twice stronger than Gd2O3 powder. Being compared with commercial Gd-DTPA/Magnevist®, Gd2O3 diethyleneglycol-coated (Gd2O3-DEG) fibers show high 1/T1 and 1/T2 proton relaxivities. Intense room temperature photoluminescence, high NMR relaxivity and high neutron scattering cross-section of 157Gd nucleus promise to integrate Gd2O3 fibers for multimodal bioimaging and neutron capture therapy.

Gadolinia nanofibers as a multimodal bioimaging and potential radiation therapy agent

Directory of Open Access Journals (Sweden)

A. M. Grishin

2015-05-01

Full Text Available Continuous bead-free C-type cubic gadolinium oxide (Gd2O3 nanofibers 20-30 μm long and 40-100 nm in diameter were sintered by sol-gel calcination assisted electrospinning technique. Dipole-dipole interaction of neighboring Gd3+ ions in nanofibers with large length-to-diameter aspect ratio results in some kind of superparamagnetic behavior: fibers are magnetized twice stronger than Gd2O3 powder. Being compared with commercial Gd-DTPA/Magnevist®, Gd2O3 diethyleneglycol-coated (Gd2O3-DEG fibers show high 1/T1 and 1/T2 proton relaxivities. Intense room temperature photoluminescence, high NMR relaxivity and high neutron scattering cross-section of 157Gd nucleus promise to integrate Gd2O3 fibers for multimodal bioimaging and neutron capture therapy.

Dose prescription in boron neutron capture therapy

International Nuclear Information System (INIS)

Gupta, N.M.S.; Gahbauer, R.A.; Blue, T.E.; Wambersie, A.

1994-01-01

The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer radiations in BNCT was proposed. The authors have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BNCT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the 10 B microdistribution in normal tissue, and the ratio of 10 B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and 10 B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of D max shifts significantly, depending on some of the treatment variables-mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. 11 refs., 6 figs., 3 tabs

Gadolinium neutron capture therapy for brain tumors. Biological aspects

International Nuclear Information System (INIS)

Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

1994-01-01

This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

Chemical warfare agents.

Science.gov (United States)

Kuca, Kamil; Pohanka, Miroslav

2010-01-01

Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

Vascular-targeted photodynamic therapy with BF2-chelated Tetraaryl-Azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment.

LENUS (Irish Health Repository)

Byrne, A T

2009-11-03

Photodynamic therapy (PDT) is a treatment modality for a range of diseases including cancer. The BF(2)-chelated tetraaryl-azadipyrromethenes (ADPMs) are an emerging class of non-porphyrin PDT agent, which have previously shown excellent photochemical and photophysical properties for therapeutic application. Herein, in vivo efficacy and mechanism of action studies have been completed for the lead agent, ADMP06.

Electrostatic design and beam transport for a folded tandem electrostatic quadrupole accelerator facility for accelerator-based boron neutron capture therapy.

Science.gov (United States)

Vento, V Thatar; Bergueiro, J; Cartelli, D; Valda, A A; Kreiner, A J

2011-12-01

Within the frame of an ongoing project to develop a folded Tandem-Electrostatic-Quadrupole (TESQ) accelerator facility for Accelerator-Based Boron Neutron Capture Therapy (AB-BNCT), we discuss here the electrostatic design of the machine, including the accelerator tubes with electrostatic quadrupoles and the simulations for the transport and acceleration of a high intensity beam. Copyright © 2011 Elsevier Ltd. All rights reserved.

Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy

DEFF Research Database (Denmark)

Pedersen-Bjergaard, J.; Specht, L.; Larsen, S.O.

1987-01-01

391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk...... of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.......0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year...

Effect of bevacizumab combined with boron neutron capture therapy on local tumor response and lung metastasis

Science.gov (United States)

MASUNAGA, SHIN-ICHIRO; SAKURAI, YOSHINORI; TANO, KEIZO; TANAKA, HIROKI; SUZUKI, MINORU; KONDO, NATSUKO; NARABAYASHI, MASARU; WATANABE, TSUBASA; NAKAGAWA, YOSUKE; MARUHASHI, AKIRA; ONO, KOJI

2014-01-01

The aim of the present study was to evaluate the effect of bevacizumab on local tumor response and lung metastatic potential during boron neutron capture therapy (BNCT) and in particular, the response of intratumor quiescent (Q) cells. B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously administered bromodeoxyuridine (BrdU) to label all proliferating (P) tumor cells. The tumors were irradiated with thermal neutron beams following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)], with or without the administration of bevacizumab. This was further combined with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH, 40°C for 60 min). Immediately following the irradiation, cells from certain tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q cells and the total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days following irradiation, lung metastases were enumerated. Three days following bevacizumab administration, the sensitivity of the total tumor cell population following BPA-BNCT had increased more than that following BSH-BNCT. The combination with MTH, but not with nicotinamide, further enhanced total tumor cell population sensitivity. Regardless of the presence of a 10B-carrier, MTH enhanced the sensitivity of the Q cell population. Regardless of irradiation, the administration of bevacizumab, as well as nicotinamide treatment, demonstrated certain potential in reducing the number of lung metastases especially in BPA-BNCT compared with BSH-BNCT. Thus, the current study revealed that BNCT combined with bevacizumab has the potential to sensitize total tumor cells and cause a reduction in the number of lung metastases to a similar level as nicotinamide. PMID:24944637

The Boron Neutron Capture Therapy (BNCT) Project at the TRIGA Reactor in Mainz, Germany

Energy Technology Data Exchange (ETDEWEB)

Hampel, G.; Grunewald, C.; Schutz, C.; Schmitz, T.; Kratz, J.V. [Nuclear Chemistry, University of Mainz, D-55099 Mainz (Germany); Brochhausen, C.; Kirkpatrick, J. [Department of Pathology, University of Mainz, D-55099 Mainz (Germany); Bortulussi, S.; Altieri, S. [Department of Nuclear and Theoretical Physics University of Pavia, Pavia (Italy); National Institute of Nuclear Physics (INFN) Pavia Section, Pavia (Italy); Kudejova, P. [Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitaet Muenchen, D-85748 Garching (Germany); Appelman, K.; Moss, R. [Joint Research Centre (JRC) of the European Commission, NL-1755 ZG Petten (Netherlands); Bassler, N. [University of Aarhus, Norde Ringade, DK-8000, Aarhus C (Denmark); Blaickner, M.; Ziegner, M. [Molecular Medicine, Health and Environment Department, AIT Austrian Institute of Technology GmbH (Austria); Sharpe, P.; Palmans, H. [National Physical Laboratory, Teddington TW11 0LW, Middlesex (United Kingdom); Otto, G. [Department of Hepatobiliary, Pancreatic and Transplantation Surgery, University of Mainz, D-55099 Mainz (Germany)

2011-07-01

The thermal column of the TRIGA reactor in Mainz is being used very effectively for medical and biological applications. The BNCT (boron neutron capture therapy) project at the University of Mainz is focussed on the treatment of liver tumours, similar to the work performed in Pavia (Italy) a few years ago, where patients with liver metastases were treated by combining BNCT with auto-transplantation of the organ. Here, in Mainz, a preclinical trial has been started on patients suffering from liver metastases of colorectal carcinoma. In vitro experiments and the first animal tests have also been initiated to investigate radiobiological effects of radiation generated during BNCT. For both experiments and the treatment, a reliable dosimetry system is necessary. From work elsewhere, the use of alanine detectors appears to be an appropriate dosimetry technique. (author)

Drug delivery system design and development for boron neutron capture therapy on cancer treatment

International Nuclear Information System (INIS)

Sherlock Huang, Lin-Chiang; Hsieh, Wen-Yuan; Chen, Jiun-Yu; Huang, Su-Chin; Chen, Jen-Kun; Hsu, Ming-Hua

2014-01-01

We have already synthesized a boron-containing polymeric micellar drug delivery system for boron neutron capture therapy (BNCT). The synthesized diblock copolymer, boron-terminated copolymers (Bpin-PLA-PEOz), consisted of biodegradable poly(D,L-lactide) (PLA) block and water-soluble polyelectrolyte poly(2-ethyl-2-oxazoline) (PEOz) block, and a cap of pinacol boronate ester (Bpin). In this study, we have demonstrated that synthesized Bpin-PLA-PEOz micelle has great potential to be boron drug delivery system with preliminary evaluation of biocompatibility and boron content. - Highlights: • Herein, we have synthesized boron-modified diblock copolymer. • Bpin-PLA-PEOz, which will be served as new boron containing vehicle for transporting the boron drug. • This boron containing Bpin-PLA-PEOz micelle was low toxicity can be applied to drug delivery

Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Xinyu Qian

Full Text Available Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.From inception to January 2015, we searched for randomized, controlled trials (RCTs using the following databases: PubMed, ScienceDirect, the Cochrane Library, Clinicaltrials.gov and EBSCO. Eligible trials included RCTs that evaluated standard chemotherapy which was either followed or not followed by targeted maintenance in patients with ovarian cancer who had been previously receiving adjunctive treatments, such as cytoreductive surgery and standard chemotherapy. The outcome measures included progression-free survival (PFS, overall survival (OS and incidence of adverse events.A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria. The primary meta-analysis indicated that both PFS and OS were statistically and significantly improved in the targeted maintenance therapy group as compared to the control group (PFS: HR = 0.84, 95%CI: 0.75 to 0.95, p = 0.001; OS: HR = 0.91, 95%CI: 0.84 to 0.98, p = 0.02. When taking safety into consideration, the use of targeted agents was significantly correlated with increased risks of fatigue, diarrhea, nausea, vomiting, and hypertension. However, no significant differences were found in incidence rates of abdominal pain, constipation or joint pain.Our results indicate that targeted maintenance therapy clearly improves the survival of ovarian cancer patients but may also increase the incidence of adverse events. Additional randomized, double-blind, placebo-controlled, multicenter investigations will be required on a larger cohort of patients to verify our findings.

Biological Tests for Boron Neutron Capture Therapy Research at the TRIGA Mark II Reactor in Pavia

Energy Technology Data Exchange (ETDEWEB)

Protti, N.; Ballarini, F.; Bortolussi, S.; De Bari, A.; Stella, S.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Nuclear Physics National Institute (INFN), Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Bakeine, J.G.; Cansolino, L.; Clerici, A.M. [Laboratory of Experimental Surgery, Department of Surgery, University of Pavia, Pavia (Italy)

2011-07-01

The thermal column of the TRIGA Mark II reactor of the Pavia University is used as an irradiation facility to perform biological tests and irradiations of living systems for Boron Neutron Capture Therapy (BNCT) research. The suitability of the facility has been ensured by studying the neutron flux and the photon background in the irradiation chamber inside the thermal column. This characterization has been realized both by flux and dose measurements as well as by Monte Carlo simulations. The routine irradiations concern in vitro cells cultures and different tumor animal models to test the efficacy of the BNCT treatment. Some results about these experiments will be described. (author)

MCNP speed advances for boron neutron capture therapy

International Nuclear Information System (INIS)

Goorley, J.T.; McKinney, G.; Adams, K.; Estes, G.

1998-04-01

The Boron Neutron Capture Therapy (BNCT) treatment planning process of the Beth Israel Deaconess Medical Center-M.I.T team relies on MCNP to determine dose rates in the subject's head for various beam orientations. In this time consuming computational process, four or five potential beams are investigated. Of these, one or two final beams are selected and thoroughly evaluated. Recent advances greatly decreased the time needed to do these MCNP calculations. Two modifications to the new MCNP4B source code, lattice tally and tracking enhancements, reduced the wall-clock run times of a typical one million source neutrons run to one hour twenty five minutes on a 200 MHz Pentium Pro computer running Linux and using the GNU FORTRAN compiler. Previously these jobs used a special version of MCNP4AB created by Everett Redmond, which completed in two hours two minutes. In addition to this 30% speedup, the MCNP4B version was adapted for use with Parallel Virtual Machine (PVM) on personal computers running the Linux operating system. MCNP, using PVM, can be run on multiple computers simultaneously, offering a factor of speedup roughly the same as the number of computers used. With two 200 MHz Pentium Pro machines, the run time was reduced to forty five minutes, a 1.9 factor of improvement over the single Linux computer. While the time of a single run was greatly reduced, the advantages associated with PVM derive from using computational power not already used. Four possible beams, currently requiring four separate runs, could be run faster when each is individually run on a single machine under Windows NT, rather than using Linux and PVM to run one after another with each multiprocessed across four computers. It would be advantageous, however, to use PVM to distribute the final two beam orientations over four computers

Monte Carlo calculations of lung dose in ORNL phantom for boron neutron capture therapy

International Nuclear Information System (INIS)

Krstic, D.; Markovic, V.M.; Jovanovic, Z.; Milenkovic, B.; Nikezic, D.; Atanackovic, J.

2014-01-01

Monte Carlo simulations were performed to evaluate dose for possible treatment of cancers by boron neutron capture therapy (BNCT). The computational model of male Oak Ridge National Laboratory (ORNL) phantom was used to simulate tumours in the lung. Calculations have been performed by means of the MCNP5/X code. In this simulation, two opposite neutron beams were considered, in order to obtain uniform neutron flux distribution inside the lung. The obtained results indicate that the lung cancer could be treated by BNCT under the assumptions of calculations. The difference in evaluated dose in cancer and normal lung tissue suggests that BNCT could be applied for the treatment of cancers. The difference in exposure of cancer and healthy tissue can be observed, so the healthy tissue can be spared from damage. An absorbed dose ratio of metastatic tissue-to-the healthy tissue was ∼5. Absorbed dose to all other organs was low when compared with the lung dose. Absorbed dose depth distribution shows that BNC therapy can be very useful in the treatments for tumour. The ratio of the tumour absorbed dose and irradiated healthy tissue absorbed dose was also ∼5. It was seen that an elliptical neutron field was better irradiation choice. (authors)

Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

Directory of Open Access Journals (Sweden)

Adam Gassas

2011-01-01

Full Text Available Background. Hyperbaric oxygen (HBO therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD. If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B mice received skin graft from CBA (H2D white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model.

Polycomplexes of Hyaluronic Acid and Borates in a Solid State and Solution: Synthesis, Characterization and Perspectives of Application in Boron Neutron Capture Therapy

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Alexander N. Zelenetskii

2018-02-01

Full Text Available In this report, we propose a new polyborate fragment synthesis strategy along the whole chain of the polysaccharide hyaluronic acid (HA to produce boron neutron capture therapy (BNCT compounds. Under high pressure and deformatory solid-state conditions, polymolecular system formation takes place due to association of phase-specific transition components into a more or less distinct microscopic organization. Fourier transform infrared (FTIR spectroscopy shows that HA and polyborates form a network of cyclic polychelate complexes. HA acts as a multidentate ligand using carboxylic and hydroxyl proton donor groups to link oxygen atoms in B–O–B bonds and borate-anions B–O(−: O–H···O, O–H···(−O. With free electron pairs in heteroatoms –O(:···B, –N(:···B, HA can act simultaneously as an electron donor. Nuclear magnetic resonance (NMR with 13C and 1H reveals a preserved complex interaction after both solubilizing and attenuating the HA-polyborate system. Stability of the product in water, low cost, ease of synthesis and scalability of manufacturing indicate that HA-polyborate complexes might have advantages over current chemotherapeutic approaches in creating therapeutic agents for BNCT.

Boron neutron capture therapy for recurrent head and neck malignancies

International Nuclear Information System (INIS)

Kato, Itsuro; Ono, Koji; Sakurai, Yoshinori

2006-01-01

To avoid severe impairment of oro-facial structures and functions, it is necessary to explore new treatments for recurrent head and neck malignancies (HNM). Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. So far for 4 years and 3 months, we have treated with 37 times of BNCT for 21 patients (14 squamous cell carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent and far advanced HNM since 2001. Results are (1) 10 B concentration of tumor/normal tissue ratio (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7, sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 6cases, PR: 11cases, PD: 3cases NE (not evaluated): 1case. Response rate was 81%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and exudates at the local lesion, improvement of PS, disappearance of ulceration, covered with normal skin and preserved oral and maxillofacial functions and tissues. (4) Survival periods after BNCT were 1-51 months (mean: 9.8 months). 4-year survival rate was 39% by Kaplan-Meier analysis. (5) A few adverse-effects such as transient mucositis, alopecia were recognized. These results indicate that BNCT represents a new and promising treatment approach for advanced HNM. (author)

Development of lithium target for accelerator based neutron capture therapy

International Nuclear Information System (INIS)

Taskaev, Sergey; Bayanov, Boris; Belov, Victor; Zhoorov, Eugene

2006-01-01

Pilot innovative accelerator based neutron source for neutron capture therapy of cancer is now of the threshold of its operation at the BINP, Russia. One of the main elements of the facility is lithium target producing neutrons via threshold 7 Li(p,n) 7 Be reaction at 25 kW proton beam with energies 1.915 MeV or 2.5 MeV. The main problems of lithium target were determined to be: 7 Be radioactive isotope activation keeping lithium layer solid, presence of photons due to proton inelastic scattering on lithium nuclei, and radiation blistering. The results of thermal test of target prototype were presented as previous NCT Congress. It becomes clear that water is preferable for cooling the target, and that lithium target 10 cm in diameter is able to run before melting. In the present report, the conception of optimal target is proposed: thin metal disk 10 cm in diameter easy for detaching, with evaporated thin layer of pure lithium from the side of proton beam exposure, its back being intensively cooled with turbulent water flow to maintain lithium layer solid. Design of the target for the neutron source constructed at BINP is shown. The results of investigation of radiation blistering and lithium layer are presented. Target unit of facility is under construction now, and obtaining neutrons is expected in nearest future. (author)

Boron neutron capture therapy for children with malignant brain tumor

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Komatsu, Hisao; Kageji, Teruyoshi; Tsuji, Fumio; Matsumoto, Keizo; Kitamura, Katsuji; Hatanaka, Hiroshi; Minobe, Takashi.

1993-01-01

Among the 131 cases with brain tumors treated by boron-neutron capture therapy (BNCT), seventeen were children. Eight supratentorial tumors included five astrocytomas(grade 2-4), two primitive neuroectodermal tumors (PNET) and one rhabdomyosarcoma. Seven pontine tumors included one astrocytoma, one PNET and 5 unverified gliomas. Two cerebellar tumors (PNET and astrocytoma) were also treated. All pontine tumors showed remarkable decrease in size after BNCT. However, most of them showed regrowth of the tumors because the neutrons were insufficient due to the depth. Four cases with cerebral tumor died of remote cell dissemination, although they all responded to BNCT. One of them survived 7 years after repeated BNCTs. An 11 years old girl with a large astrocytoma in the right frontal lobe has lived more than 11 years and is now a draftswoman at a civil engineering company after graduating from a technical college. An 8 years old girl with an astrocytoma in the left occipital lobe has no recurrence of the tumor for 2 years and attends on elementary school without mental and physical problems. Two children (one year old girl and four years old boy) with cerebellar tumors have shown showed an excellent growth after BNCT and had no neurological deficits. Mental and physical development in patients treated by BNCT is usually better than that in patients treated by conventional radiotherapy. (author)

Contributions of nuclear medicine to the therapy of malignant tumors

Energy Technology Data Exchange (ETDEWEB)

Feinendegen, L.E. (Forschungszentrum Juelich GmbH (Germany). Inst. fuer Medizin Duesseldorf Univ. (Germany). Nuklearmedizinische Klinik)

1991-11-01

The diagnostic and therapeutic application of radionuclides on oncology has led to an increased efficiency in the treatment of malignant tumors. - Regarding diagnosis, measuring metabolic reactions in tumor tissue, especially by positron emission tomography, opened the potential for assaying tumor response to different treatment modalities and thus eventually for tailoring effective treatment of a given tumor in the individual patient. - Regarding treatment, attention is given to the choice of the radionuclide for optimal deposition of the desired radiation in tumor cells avoiding exposure of normal cells; in this context microdosimetric considerations are essential with respect to {beta}-emitters, {alpha}-emitters, the Auger-effect and neutron capture therapy. Examples of therapeutic uses of radionuclides in the inorganic form are 131-I for thyroid cancer and 32-P for polycythemia vera; organically bound radionuclides are employed with precursors for tumor cell metabolism or with receptor seeking agents, such as MIBG and monoclonal antibodies which presently enjoy a particular interest and bear great promise. Stable nuclides, if property accumulated within tumors, may be activated for therapy in situ, for example by thermal neutrons, as in neutron capture therapy using the 10-B (n, {alpha})7-Li reaction. - Treatment planning and execution with radionuclides have gained momentum over the past decade, yet much more needs to be done. (orig.).

In vitro and in vivo studies in boron neutron capture therapy of malignant melanoma

International Nuclear Information System (INIS)

Allen, B.J.

1982-01-01

A multidisciplinary research project in boron neutron capture therapy of malignant melanoma is under consideration by the Australian Atomic Energy Commission. This paper reviews the biochemistry of melanoma and the properties of some melanoma-affined radiopharmaceuticals and their boron analogues. Human cell lines are being used for in vitro tests of uptake and incorporation of some of these compounds, and selected lines will then be implanted in nude mice for in vivo distribution studies. The fidelity of human melanoma xenografts in nude mice has been well studied, and results are reviewed in this paper. Boron concentration will be measured directly by plasma arc emission spectroscopy or liquid scintillation counting with 14 C-labelled boron analogues. Track-etch techniques will be used for the microscopic determination of boron in tumor sections. Neutron irradiation and radiobiology experiments are outlined

Clinical trials of boron neutron capture therapy [in humans] [at Beth Israel Deaconess Medical Center][at Brookhaven National Laboratory

International Nuclear Information System (INIS)

Wallace, Christine

2001-01-01

Assessment of research records of Boron Neutron Capture Therapy was conducted at Brookhaven National Laboratory and Beth Israel Deaconess Medical Center using the Code of Federal Regulations, FDA Regulations and Good Clinical Practice Guidelines. Clinical data were collected FR-om subjects' research charts, and differences in conduct of studies at both centers were examined. Records maintained at Brookhaven National Laboratory were not in compliance with regulatory standards. Beth Israel's records followed federal regulations. Deficiencies discovered at both sites are discussed in the reports

Accelerator conceptual design and needs of nuclear data for boron neutron capture therapy

International Nuclear Information System (INIS)

Sasaki, Makoto; Yamanaka, Toshiyuki; Yokobori, Hitoshi

1999-01-01

An optimization study has been made on an accelerator-based facility for the boron neutron capture therapy. The energy of the incident proton and the arrangement of the moderator assemblies are optimized. The beam current and the accelerating voltage are determined so that the accelerator power becomes minimum. The proposed facility is equipped with a 2.5 MeV proton accelerator of 10-25 mA, a lithium target, and a heavy water moderator contained in an aluminum tank. Each of these equipment is feasible, if proper R and D works have been done. Our new design requires the beam power of less than a hundred kW for the accelerator, although that of our previous design was 1 MW. The reduction of the beam power makes the cooling system for the target much simpler. The essential issues for realization of this concept are long-life lithium targets under high heat flux and high current proton accelerators with average currents of more than 10 mA. It is necessary for the reasonable design of a small-sized and low cost facility to get good accuracy nuclear reaction data. Especially, the latest Li/Be(p, n) neutron yield data in a range of threshold energy - few MeV are required for exact evaluation of neutron energy spectrum used therapy. And damage data by low energy proton beam are also important to evaluate integrity of target material. (author)

Small molecules as therapy for uveitis: a selected perspective of new and developing agents.

Science.gov (United States)

Pleyer, Uwe; Algharably, Engi Abdel-Hady; Feist, Eugen; Kreutz, Reinhold

2017-09-01

Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis. Areas covered: A MEDLINE database search was conducted through February 2017 using the terms 'uveitis' and 'small molecule'. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Both, results from experimental as well as clinical research in this field were included. Since this field is rapidly evolving, a selection of promising agents had to be made. Expert opinion: Small molecules may interfere at different steps of the inflammatory cascade and appear as an interesting option in the treatment algorithm of uveitis. Because of their highly targeted molecular effects and their favorable bioavailability with the potential of topical application small molecules hold great promise. Nevertheless, a careful evaluation of these agents has to be made, since current experience is almost exclusively based on experimental uveitis models and few registered trials.

Gadolinia nanofibers as a multimodal bioimaging and potential radiation therapy agent

Energy Technology Data Exchange (ETDEWEB)

Grishin, A. M., E-mail: grishin@kth.se, E-mail: grishin@inmatech.com [KTH Royal Institute of Technology, SE-164 40 Stockholm-Kista (Sweden); INMATECH Intelligent Materials Technology, SE-127 45 Skärholmen (Sweden); Petrozavodsk State University, 185910 Petrozavodsk, Karelian Republic (Russian Federation); Jalalian, A. [KTH Royal Institute of Technology, SE-164 40 Stockholm-Kista (Sweden); INMATECH Intelligent Materials Technology, SE-127 45 Skärholmen (Sweden); Tsindlekht, M. I. [Racah Institute of Physics, Hebrew University of Jerusalem, 91904 Jerusalem (Israel)

2015-05-15

Continuous bead-free C-type cubic gadolinium oxide (Gd{sub 2}O{sub 3}) nanofibers 20-30 μm long and 40-100 nm in diameter were sintered by sol-gel calcination assisted electrospinning technique. Dipole-dipole interaction of neighboring Gd{sup 3+} ions in nanofibers with large length-to-diameter aspect ratio results in some kind of superparamagnetic behavior: fibers are magnetized twice stronger than Gd{sub 2}O{sub 3} powder. Being compared with commercial Gd-DTPA/Magnevist{sup ®}, Gd{sub 2}O{sub 3} diethyleneglycol-coated (Gd{sub 2}O{sub 3}-DEG) fibers show high 1/T{sub 1} and 1/T{sub 2} proton relaxivities. Intense room temperature photoluminescence, high NMR relaxivity and high neutron scattering cross-section of {sup 157}Gd nucleus promise to integrate Gd{sub 2}O{sub 3} fibers for multimodal bioimaging and neutron capture therapy.

Gold Nanoparticles as a Photothermal Agent in Cancer Therapy: The Thermal Ablation Characteristic Length

Directory of Open Access Journals (Sweden)

Thomas Grosges

2018-05-01

Full Text Available In cancer therapy, the thermal ablation of diseased cells by embedded nanoparticles is one of the known therapies. It is based on the absorption of the energy of the illuminating laser by nanoparticles. The resulting heating of nanoparticles kills the cell where these photothermal agents are embedded. One of the main constraints of this therapy is preserving the surrounding healthy cells. Therefore, two parameters are of interest. The first one is the thermal ablation characteristic length, which corresponds to an action distance around the nanoparticles for which the temperature exceeds the ablation threshold. This critical geometric parameter is related to the expected conservation of the body temperature in the surroundings of the diseased cell. The second parameter is the temperature that should be reached to achieve active thermal agents. The temperature depends on the power of the illuminating laser, on the size of nanoparticles and on their physical properties. The purpose of this paper is to propose behavior laws under the constraints of both the body temperature at the boundary of the cell to preserve surrounding cells and an acceptable range of temperature in the target cell. The behavior laws are deduced from the finite element method, which is able to model aggregates of nanoparticles. We deduce sensitivities to the laser power and to the particle size. We show that the tuning of the temperature elevation and of the distance of action of a single nanoparticle is not significantly affected by variations of the particle size and of the laser power. Aggregates of nanoparticles are much more efficient, but represent a potential risk to the surrounding cells. Fortunately, by tuning the laser power, the thermal ablation characteristic length can be controlled.

The Effect of Deep Brain Stimulation Therapy on Fear-Related Capture of Attention in Parkinson's Disease and Essential Tremor: A Comparison to Healthy Individuals.

Science.gov (United States)

Camalier, Corrie R; McHugo, Maureen; Zald, David H; Neimat, Joseph S

2018-01-01

In addition to motor symptoms, Parkinson's disease (PD) involves significant non-motor sequelae, including disruptions in cognitive and emotional processing. Fear recognition appears to be affected both by the course of the disease and by a common interventional therapy, deep brain stimulation of the subthalamic nucleus (STN-DBS). Here, we examined if these effects extend to other aspects of emotional processing, such as attentional capture by negative emotional stimuli. Performance on an emotional attentional blink (EAB) paradigm, a common paradigm used to study emotional capture of attention, was examined in a cohort of individuals with PD, both on and off STN-DBS therapy (n=20). To contrast effects of healthy aging and other movement disorder and DBS targets, we also examined performance in a healthy elderly (n=20) and young (n=18) sample on the same task, and a sample diagnosed with Essential Tremor (ET) undergoing therapeutic deep brain stimulation of the ventral-intermediate nucleus (VIM-DBS, n=18). All four groups showed a robust attentional capture of emotional stimuli, irrespective of aging processes, movement disorder diagnosis, or stimulation. PD patients on average had overall worse performance, but this decrement in performance was not related to the emotional capture of attention. PD patients exhibited a robust EAB, indicating that the ability of emotion to direct attention remains intact in PD. Congruent with other recent data, these findings suggest that fear recognition deficits in PD may instead reflect a highly specific problem in recognition, rather than a general deficit in emotional processing of fearful stimuli.

General Video Game AI: Learning from Screen Capture

OpenAIRE

Kunanusont, Kamolwan; Lucas, Simon M.; Perez-Liebana, Diego

2017-01-01

General Video Game Artificial Intelligence is a general game playing framework for Artificial General Intelligence research in the video-games domain. In this paper, we propose for the first time a screen capture learning agent for General Video Game AI framework. A Deep Q-Network algorithm was applied and improved to develop an agent capable of learning to play different games in the framework. After testing this algorithm using various games of different categories and difficulty levels, th...

Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy

Directory of Open Access Journals (Sweden)

Schaffran T

2014-07-01

Full Text Available Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine, University of Bremen, 4“In-vivo-MR” AG, FB2, University of Bremen, Bremen, 5Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, 6Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II, Technische Unversitaet Muenchen, Garching, Germany; 7Department of Biochemistry, Alexandria University, Alexandria, Egypt; 8School of Engineering and Science, Jacobs University Bremen, Bremen, Germany Abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma. With the exception of one lipid (B-THF-14, the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids

Early effects of boron neutron capture therapy on rat glioma models

International Nuclear Information System (INIS)

Nakagawa, N.; Akai, F.; Fukawa, N.; Taneda, M.; Ono, K.; Suzuki, M.

2006-01-01

Early effects of boron neutron capture therapy on malignant gliomas are characterized by reduction of the enhanced area regression of the peritumoral edema radiologically. The aim of this study is to investigate the early histological changes of tumors and inflammatory cells after BNCT in the rat brain. The rats were treated with BNCT using boronophenyialanine (BPA) 7 days after implantation of C6 glioma cells. The tumors were assessed their sizes and configurations with magnetic resonance imaging, then killed 4 days after BNCT. The mean tumor volumes were 39mm 3 in BNCT-treated group, and 138 mm 3 in the control group. In the histological examination, tumors of the BNCT group showed less pleomorphic appearance with atypical nuclei and mitotic figures, compared with the control group. Necrosis and edematous changes in the neuropile were negligible. There existed remnant tumors adjacent to the lateral ventricle. The reactions of the inflammatory cells were examined with ED-1 of macrophage marker. ED-1 positive cells and their processes were reduced in the marginal area of tumor in the BNCT group. BNCT reduce the tumor progression by suppression of the proliferation. Inhibition of the activated macrophages may reduce peritumoral edema in early phase. (author)

Development of reference problems for neutron capture therapy treatment planning systems

International Nuclear Information System (INIS)

Albritton, J.R.; Kiger, W.S. III

2006-01-01

Currently, 5 different treatment planning systems (TPSs) are or have been used in clinical trials of Neutron Capture Therapy (NCT): MacNCTPlan, NCTPlan, BNCT Rtpe, SERA, and JCDS. This paper describes work performed to comprehensively test and compare 4 of these NCT treatment planning systems in order to facilitate the pooling of patient data from the different clinical sites for analysis of the clinical results as well as to provide an important quality assurance tool for existing and future TPSs. Two different phantoms were used to evaluate the planning systems: the modified Snyder head phantom and a large water-filled box, similar to that used in the International Dosimetry Exchange for NCT. The comparison of the resulting dose profile, isodose contours, and dose volume histograms to reference calculations performed with the Monte Carlo radiation transport code MCNP5 yielded many interesting differences. Each of the planning systems deviated from the reference calculations, with the newer systems (i.e., SERA and NCTPlan) most often yielding better agreement than their predecessors (i.e., BNCT Rtpe and MacNCTPlan). The combination of simple phantoms and sources with more complicated and realistic planning conditions has produced a well-rounded and useful suite of test problems for NCT treatment planning system analysis. (author)

Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha conjugated gold nanoparticles for multimodal cancer therapy.

Science.gov (United States)

Shenoi, Mithun M; Iltis, Isabelle; Choi, Jeunghwan; Koonce, Nathan A; Metzger, Gregory J; Griffin, Robert J; Bischof, John C

2013-05-06

Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1-2 h followed by a dramatic 80% drop in perfusion 2-6 h after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the sub- and supraphysiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult in a targeted

A smart drug: a pH-responsive photothermal ablation agent for Golgi apparatus activated cancer therapy.

Science.gov (United States)

Xue, Fengfeng; Wen, Ying; Wei, Peng; Gao, Yilin; Zhou, Zhiguo; Xiao, Shuzhang; Yi, Tao

2017-06-13

We report a pH-responsive photothermal ablation agent (pH-PTT) based on cyanine dyes for photothermal therapy (PTT). The nanoparticles formed by BSA and pH-PTT preferentially accumulated in the Golgi apparatus of cancer cells compared to normal cells, and thus can be specifically activated by the acidic Golgi apparatus in cancer cells for effective PTT both ex vivo and in vivo.

Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy

International Nuclear Information System (INIS)

Bergueiro, J.; Igarzabal, M.; Suarez Sandin, J.C.; Somacal, H.R.; Thatar Vento, V.; Huck, H.; Valda, A.A.; Repetto, M.

2011-01-01

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes.

Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy

Energy Technology Data Exchange (ETDEWEB)

Bergueiro, J. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [CONICET, Buenos Aires (Argentina); Igarzabal, M.; Suarez Sandin, J.C. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina); Somacal, H.R. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina); Thatar Vento, V. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [CONICET, Buenos Aires (Argentina); Huck, H.; Valda, A.A. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)] [Escuela de Ciencia y Tecnologia, Universidad Nacional de San Martin (Argentina); Repetto, M. [Gerencia de Investigacion y Aplicaciones, Comision Nacional de Energia Atomica (Argentina)

2011-12-15

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes.

Boron neutron capture therapy (BNCT) for glioblastoma multiforme using the epithermal neutron beam at the Brookhaven Medical Research Reactor

International Nuclear Information System (INIS)

Capala, J.; Diaz, A.Z.; Chadha, M.

1997-01-01

The abstract describes evaluation of boron neutron capture therapy (BNCT) for two groups of glioblastoma multiforme patients. From September 1994 to February 1996 15 patients have been treated. In September 1997 another 34 patients were examined. Authors determined a safe starting dose for BNCT using epithermal neutrons and BPA-F. They have also evaluated adverse effects of BNCT at this starting dose. Therapeutic effectiveness of this starting dose has been evaluated. No significant side effects from BPA-F infusion or BNCT treatment were observed in normal brains

Boron neutron capture therapy (BNCT) for glioblastoma multiforme using the epithermal neutron beam at the Brookhaven Medical Research Reactor

Energy Technology Data Exchange (ETDEWEB)

Capala, J. [Brookhaven National Lab., Upton, NY (United States); Diaz, A.Z.; Chadha, M. [Univ. Hospital, State Univ. of New York, NY (United States)] [and others

1997-12-31

The abstract describes evaluation of boron neutron capture therapy (BNCT) for two groups of glioblastoma multiforme patients. From September 1994 to February 1996 15 patients have been treated. In September 1997 another 34 patients were examined. Authors determined a safe starting dose for BNCT using epithermal neutrons and BPA-F. They have also evaluated adverse effects of BNCT at this starting dose. Therapeutic effectiveness of this starting dose has been evaluated. No significant side effects from BPA-F infusion or BNCT treatment were observed in normal brains.

Study on high speed lithium jet for neutron source of boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Takahashi, Minoru; Kobayashi, Tooru; Zhang, Mingguang; Mak, Michael; Stefanica, Jiri; Dostal, Vaclav; Zhao Wei

2012-01-01

The feasibility study of a liquid lithium type proton beam target was performed for the neutron source of the boron neutron capture therapy (BNCT). As the candidates of the liquid lithium target, a thin sheet jet and a thin film flow on a concave wall were chosen, and a lithium flow experiment was conducted to investigate the hydrodynamic stability of the targets. The surfaces of the jets and film flows with a thickness of 0.5 mm and a width of 50 mm were observed by means of photography. It has been found that a stable sheet jet and a stable film flow on a concave wall can be formed up to certain velocities by using a straight nozzle and a curved nozzle with the concave wall, respectively. (author)

Molecular Targeted Agents for Gastric Cancer: A Step Forward Towards Personalized Therapy

Directory of Open Access Journals (Sweden)

Tom Geldart

2013-01-01

Full Text Available Gastric cancer (GC represents a major cancer burden worldwide, and remains the second leading cause of cancer-related death. Due to its insidious nature, presentation is usually late and often carries a poor prognosis. Despite having improved treatment modalities over the last decade, for most patients only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and its signaling pathways, offers the hope of clinically significant promising advances for selected groups of patients. Patients with Her-2 overexpression or amplification have experienced benefit from the integration of monoclonal antibodies such as trastuzumab to the standard chemotherapy. Additionally, drugs targeting angiogenesis (bevacizumab, sorafenib, sunitinib are under investigation and other targeted agents such as mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors are in preclinical or early clinical development. Patient selection and the development of reliable biomarkers to accurately select patients most likely to benefit from these tailored therapies is now key. Future trials should focus on these advances to optimize the treatment for GC patients. This article will review recent progress and current status of targeted agents in GC.

Clinical potential of boron neutron capture therapy for locally recurrent inoperable previously irradiated head and neck cancer

International Nuclear Information System (INIS)

Lim, Diana; Quah, Daniel SC; Leech, Michelle; Marignol, Laure

2015-01-01

This review compares the safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of previously irradiated, inoperable locoregional recurrent HNC patients and compares BNCT against the standard treatment of platinum-based chemotherapy. Our analysis of published clinical trials highlights efficacy of BNCT associated with mild side effects. However, the use of BNCT should be explored in stratified randomised trials. - Highlights: • BNCT can prolong median overall survival. • BNCT can be associated with severe adverse effects. • BNCT may be comparable to chemotherapy-based regimens. • BNCT may be comparable to re-irradiation techniques regimens in patients with low performance status.

Comparison of two brain tumor-localizing MRI agent. GD-BOPTA and GD-DTPA. MRI and ICP study of rat brain tumor model

International Nuclear Information System (INIS)

Zhang, T.; Matsumura, A.; Yamamoto, T.; Yoshida, F.; Nose, T.

2000-01-01

In this study, we compared the behavior of Gd-BOPTA as a brain tumor selective contrast agent with Gd-DTPA in a common dose of 0.1 mmol/kg. We performed a MRI study using those two agent as contrast material, and we measured tissue Gd-concentrations by ICP-AES. As a result, Gd-BOPTA showed a better MRI enhancement in brain tumor. ICP showed significantly greater uptake of Gd-BOPTA in tumor samples, at all time course peaked at 5 minutes after administration, Gd being retained for a longer time in brain tumor till 2 hours, without rapid elimination as Gd-DTPA. We conclude that Gd-BOPTA is a new useful contrast material for MR imaging in brain tumor and an effective absorption agent for neutron capture therapy for further research. (author)

A theoretical model for the production of Ac-225 for cancer therapy by neutron capture transmutation of Ra-226.

Science.gov (United States)

Melville, G; Melville, P

2013-02-01

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation by bombarding Ra-226 with high-energy neutrons from a neutron source to produce Ra-225 and hence Ac-225, which can be used as a generator to produce Bi-213 for use in 'Targeted Alpha Therapy' for cancer. This paper examines the possibility of producing Ac-225 by neutron capture using a theoretical model in which neutron energy is convoluted with the corresponding neutron cross sections of Ra-226. The total integrated yield can then be obtained. This study shows that an intense beam of high-energy neutrons could initiate neutron capture on Ra-226 to produce Ra-225 and hence practical amounts of Ac-225 and a useful reduction of Ra-226. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

International Nuclear Information System (INIS)

Beal, Kathryn; Abrey, Lauren E; Gutin, Philip H

2011-01-01

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

MODELING THE RADIATION SHIELDING OF BORON NEUTRON CAPTURE THERAPY BASED ON 2.4 MEV D-D NEUTRON GENERATOR FACILITY

Directory of Open Access Journals (Sweden)

Muhammad Mu’Alim

2018-01-01

PEMODELAN PERISAI RADIASI PADA FASILITAS BORON NEUTRON CAPTURE THERAPY BERBASIS GENERATOR NEUTRON D-D 2,4 MeV. Telah dimodelkan perisai radiasi pada fasilitas Boron Neutron Capture Therapy (BNCT berbasis reaksi D-D pada Neutron Generator 2,4 MeV dengan Beam Shaping Assembly (BSA yang telah didesain sebelumnya. Pemodelan ini dilakukan untuk memperoleh suatu desain perisai radiasi untuk fasilitas BNCT berbasis generator neutron 2,4 MeV. Pemodelan dilakukan dengan cara memvariasikan bahan dan ketebalan perisasi radiasi. Bahan yang dipilih adalah beton barit, parafin, polietilen terborasi dan timbal. Perhitungan dilakukan menggunakan program MCNPX dengan tally F4 untuk menentukan laju dosis yang keluar dari perisai radiasi. Desain periasi radiasi dinyatakan optimal jika radiasi yang dihasilkan diluar perisai radiasi tidak melebihi Nilai Batas Dosis (NBD yang telah ditentukan oleh BAPETEN. Hasilnya, diperoleh suatu desain perisai radiasi menggunakan lapisan utama beton barit setebal 100 cm yang mengelilingi ruangan 100 cm x 100 cm x 166,4 cm dan polietilen terborasi 40 cm yang mengelilingi bahan beton barit. Kemudian ditambahkan beton barit 10 cm dan polietilen terborasi 10 cm untuk mengurangi radiasi primer yang lurus dari BSA setelah keluar dari lapisan utama. Laju dosis terbesar adalah 4,58 μSv·jam-1 pada sel 227 dan laju dosis rata-rata yang dihasilkan adalah sebesar 0,65 µSv·jam-1. Nilai laju dosis tersebut masih dibawah ambang batas NBD yang diperbolehkan oleh BAPETEN untuk pekerja radiasi. Kata kunci: Perisai radiasi, tally, laju dosis radiasi, BSA, BNCT

Boron analysis for neutron capture therapy using particle-induced gamma-ray emission

International Nuclear Information System (INIS)

Nakai, Kei; Yamamoto, Yohei; Okamoto, Emiko; Yamamoto, Tetsuya; Yoshida, Fumiyo; Matsumura, Akira; Yamada, Naoto; Kitamura, Akane; Koka, Masashi; Satoh, Takahiro

2015-01-01

The neutron source of BNCT is currently changing from reactor to accelerator, but peripheral facilities such as a dose-planning system and blood boron analysis have still not been established. To evaluate the potential application of particle-induced gamma-ray emission (PIGE) for boron measurement in clinical boron neutron capture therapy, boronophenylalanine dissolved within a cell culture medium was measured using PIGE. PIGE detected 18 μgB/mL f-BPA in the culture medium, and all measurements of any given sample were taken within 20 min. Two hours of f-BPA exposure was required to create a boron distribution image. However, even though boron remained in the cells, the boron on the cell membrane could not be distinguished from the boron in the cytoplasm. - Highlights: • PIGE was evaluated for measuring blood boron concentration during clinical BNCT. • PIGE detected 18 μgB/mL f-BPA in culture medium. • All measurements of any given sample were taken within 20 min. • Two hours of f-BPA exposure is required to create boron distribution image by PIGE. • Boron on the cell membrane could not be distinguished from boron in the cytoplasm.

Removal of Hg(II) from aqueous solution using sodium humate as heavy metal capturing agent.

Science.gov (United States)

Wang, Shixiang; Liu, Yong; Fan, Qin; Zhou, Anlan; Fan, Lu; Mu, Yulan

2016-12-01

An environmental friendly and economic natural biopolymer-sodium humate (HA-Na) was used to capture Hg(II) from aqueous solutions, and the trapped Hg(II) (HA-Na-Hg) was then removed by aluminium coagulation. The best Hg(II) capturing performance (90.60%) was observed under the following conditions: initial pH of 7.0, coagulation pH of 6.0, HA-Na dosage of 5.0 g L -1 , Al 2 (SO 4 ) 3 .18H 2 O dosage of 4.0 g L -1 , initial Hg(II) concentration of 50 mg L -1 and capturing time of 30 min. The HA-Na compositions with the molecular weight beyond 70 kDa showed the most intense affinity toward Hg(II). The results showed that the reaction equilibrium was achieved within 10 min (pH 7.0), and could be well fitted by the pseudo-second-order kinetics model. The capturing process could be well described by the Langmuir isotherm model and the maximum capturing capacity of Hg(II) was high up to 9.80 mg g -1 at 298 K (pH 7.0). The Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis showed that the redox reaction between Hg(II) and HA-Na and the coordination reaction of carboxyl and hydroxy groups of HA-Na with Hg(II) were responsible for Hg(II) removal. The successive regeneration experiment showed that the capturing efficiency of humates for Hg(II) was maintained at about 51% after five capture-regeneration recycles.

[Decorporation agents for internal radioactive contamination].

Science.gov (United States)

Ohmachi, Yasushi

2015-01-01

When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented.

Boron neutron capture therapy of intracerebral rat gliosarcomas

International Nuclear Information System (INIS)

Joel, D.D.; Fairchild, R.G.; Laissue, J.A.; Saraf, S.K.; Kalef-Ezra, J.A.; Slatkin, D.N.

1990-01-01

The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation

Patients with advanced and metastatic renal cell carcinoma treated with targeted therapy in the Czech Republic: twenty cancer centres, six agents, one database.

Science.gov (United States)

Poprach, Alexandr; Bortlíček, Zbyněk; Büchler, Tomáš; Melichar, Bohuslav; Lakomý, Radek; Vyzula, Rostislav; Brabec, Petr; Svoboda, Marek; Dušek, Ladislav; Gregor, Jakub

2012-12-01

The incidence and mortality of renal cell carcinoma (RCC) in the Czech Republic are among the highest in the world. Several targeted agents have been recently approved for the treatment of advanced/metastatic RCC. Presentation of a national clinical database for monitoring and assessment of patients with advanced/metastatic RCC treated with targeted therapy. The RenIS (RENal Information System, http://renis.registry.cz ) registry is a non-interventional post-registration database of epidemiological and clinical data of patients with RCC treated with targeted therapies in the Czech Republic. Twenty cancer centres eligible for targeted therapy administration participate in the project. As of November 2011, six agents were approved and reimbursed from public health insurance, including bevacizumab, everolimus, pazopanib, sorafenib, sunitinib, and temsirolimus. As of 10 October 2011, 1,541 patients with valid records were entered into the database. Comparison with population-based data from the Czech National Cancer Registry revealed that RCC patients treated with targeted therapy are significantly younger (median age at diagnosis 59 vs. 66 years). Most RenIS registry patients were treated with sorafenib and sunitinib, many patients sequentially with both agents. Over 10 % of patients were also treated with everolimus in the second or third line. Progression-free survival times achieved were comparable to phase III clinical trials. The RenIS registry has become an important tool and source of information for the management of cancer care and clinical practice, providing comprehensive data on monitoring and assessment of RCC targeted therapy on a national level.

Development of high intensity ion sources for a Tandem-Electrostatic-Quadrupole facility for Accelerator-Based Boron Neutron Capture Therapy.

Science.gov (United States)

Bergueiro, J; Igarzabal, M; Sandin, J C Suarez; Somacal, H R; Vento, V Thatar; Huck, H; Valda, A A; Repetto, M; Kreiner, A J

2011-12-01

Several ion sources have been developed and an ion source test stand has been mounted for the first stage of a Tandem-Electrostatic-Quadrupole facility For Accelerator-Based Boron Neutron Capture Therapy. A first source, designed, fabricated and tested is a dual chamber, filament driven and magnetically compressed volume plasma proton ion source. A 4 mA beam has been accelerated and transported into the suppressed Faraday cup. Extensive simulations of the sources have been performed using both 2D and 3D self-consistent codes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Study on the dose distribution of the mixed field with thermal and epi-thermal neutrons for neutron capture therapy

International Nuclear Information System (INIS)

Kobayashi, Tooru; Sakurai, Yoshinori; Kanda, Keiji

1994-01-01

Simulation calculations using DOT 3.5 were carried out in order to confirm the characteristics of depth-dependent dose distribution in water phantom dependent on incident neutron energy. The epithermal neutrons mixed to thermal neutron field is effective improving the thermal neutron depth-dose distribution for neutron capture therapy. A feasibility study on the neutron energy spectrum shifter was performed using ANISN-JR for the KUR Heavy Water Facility. The design of the neutron spectrum shifter is feasible, without reducing the performance as a thermal neutron irradiation field. (author)

The Efficacy of Single-Agent Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Biologically Selected Patients with Non-Small-Cell Lung Cancer: A Meta-Analysis of 19 Randomized Controlled Trials.

Science.gov (United States)

Li, Guifang; Gao, Shunji; Sheng, Zhixin; Li, Bin

2016-01-01

To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis. We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single-agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients. © 2016 S. Karger AG, Basel.

A Small-Animal Irradiation Facility for Neutron Capture Therapy Research at the RA-3 Research Reactor

Energy Technology Data Exchange (ETDEWEB)

Emiliano Pozzi; David W. Nigg; Marcelo Miller; Silvia I. Thorp; Amanda E. Schwint; Elisa M. Heber; Veronica A. Trivillin; Leandro Zarza; Guillermo Estryk

2007-11-01

The National Atomic Energy Commission of Argentina (CNEA) has constructed a thermal neutron source for use in Boron Neutron Capture Therapy (BNCT) applications at the RA-3 research reactor facility located in Buenos Aires. The Idaho National Laboratory (INL) and CNEA have jointly conducted some initial neutronic characterization measurements for one particular configuration of this source. The RA-3 reactor (Figure 1) is an open pool type reactor, with 20% enriched uranium plate-type fuel and light water coolant. A graphite thermal column is situated on one side of the reactor as shown. A tunnel penetrating the graphite structure enables the insertion of samples while the reactor is in normal operation. Samples up to 14 cm height and 15 cm width are accommodated.

Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy.

Science.gov (United States)

Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred

2008-11-25

Boron neutron capture therapy (BNCT) is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of (10)B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots) to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

Folate Functionalized Boron Nitride Nanotubes and their Selective Uptake by Glioblastoma Multiforme Cells: Implications for their Use as Boron Carriers in Clinical Boron Neutron Capture Therapy

Directory of Open Access Journals (Sweden)

Ciofani Gianni

2008-01-01

Full Text Available Abstract Boron neutron capture therapy (BNCT is increasingly being used in the treatment of several aggressive cancers, including cerebral glioblastoma multiforme. The main requirement for this therapy is selective targeting of tumor cells by sufficient quantities of10B atoms required for their capture/irradiation with low-energy thermal neutrons. The low content of boron targeting species in glioblastoma multiforme accounts for the difficulty in selective targeting of this very malignant cerebral tumor by this radiation modality. In the present study, we have used for the first time boron nitride nanotubes as carriers of boron atoms to overcome this problem and enhance the selective targeting and ablative efficacy of BNCT for these tumors. Following their dispersion in aqueous solution by noncovalent coating with biocompatible poly-l-lysine solutions, boron nitride nanotubes were functionalized with a fluorescent probe (quantum dots to enable their tracking and with folic acid as selective tumor targeting ligand. Initial in vitro studies have confirmed substantive and selective uptake of these nanovectors by glioblastoma multiforme cells, an observation which confirms their potential clinical application for BNCT therapy for these malignant cerebral tumors.

Synergistic combination therapy of antitumor agents, membrane modification agents and irradiation

International Nuclear Information System (INIS)

Watarai, Jiro; Itagaki, Takatomo; Akutsu, Thoru; Yamaguchi, Kouichi; Kato, Isao

1983-01-01

Larygeal cancer were treated with synergistic combination therapy of Futraful in suppository, vitamin A, cepharanthin and irradiation from April 1981 to June 1982. This combination therapy resulted in high percentage of the tumor regression in the case of the invading laryngeal cancer and negligible complication. (author)

A study on the utilization of hyper-thermal neutrons for neutron capture therapy

International Nuclear Information System (INIS)

Sakurai, Yoshinori; Kobayashi, Tooru; Kanda, Keiji

1993-01-01

The utilization of hyper-thermal neutrons, which have an energy spectrum of a Maxwellian distribution of a higher temperature than the room temperature of 300 K, was studied in order to improve the thermal neutron flux distribution at the deeper part in a living body for neutron capture therapy. Simulation calculations were carried out using MCNP-V3 in order to confirm the characteristics of hyper-thermal neutrons, i.e., (1) depth dependence of neutron energy spectrum, and (2) depth distribution of the reaction rate in a water phantom for materials with 1/v neutron absorption. It is confirmed that the hyper-thermal neutron irradiation can improve the thermal neutron flux distribution in the deeper and wider area in a living body compared with the thermal neutron irradiation. Practically, by the incidence of the hyper-thermal neutrons with a 3000 K Maxwellian distribution, the thermal neutron flux at 5 cm depth can be given about four times larger than by the incidence of the thermal neutrons of 300 K. (author)

[Alkylating agents].

Science.gov (United States)

Pourquier, Philippe

2011-11-01

With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS)

Science.gov (United States)

Chandra, S.; Ahmad, T.; Barth, R. F.; Kabalka, G. W.

2014-01-01

Boron neutron capture therapy (BNCT) of cancer depends on the selective delivery of a sufficient number of boron-10 (10B) atoms to individual tumor cells. Cell killing results from the 10B (n, α)7Li neutron capture and fission reactions that occur if a sufficient number of 10B atoms are localized in the tumor cells. Intranuclear 10B localization enhances the efficiency of cell killing via damage to the DNA. The net cellular content of 10B atoms reflects both bound and free pools of boron in individual tumor cells. The assessment of these pools, delivered by a boron delivery agent, currently cannot be made at subcellular scale resolution by clinically applicable techniques such as PET and MRI. In this study, secondary ion mass spectrometry (SIMS) based imaging instrument, a CAMECA IMS 3f ion microscope, capable of 500 nm spatial resolution was employed. Cryogenically prepared cultured human T98G glioblastoma cells were evaluated for boron uptake and retention of two delivery agents. The first, L-p-boronophenylalanine (BPA), has been used clinically for BNCT of high grade gliomas, recurrent tumors of the head and neck region and melanomas. The second, a boron analogue of an unnatural amino acid, 1-amino-3-borono-cyclopentanecarboxylic acid (cis-ABCPC), has been studied in rodent glioma and melanoma models by quantification of boron in the nucleus and cytoplasm of individual tumor cells. The bound and free pools of boron were assessed by exposure of cells to boron-free nutrient medium. Both BPA and cis-ABCPC delivered almost 70% of the pool of boron in the free or loosely bound form to the nucleus and cytoplasm of human glioblastoma cells. This free pool of boron could be easily mobilized out of the cell and was in some sort of equilibrium with extracellular boron. In the case of BPA, the intracellular free pool of boron also was affected by the presence of phenylalanine in the nutrient medium. This suggests that it might be advantageous if patients were placed on a

Study of the interaction of boron-containing amino acids for the neutron capture therapy with biologically interesting compounds by using 'three-spot zone electrophoresis'

International Nuclear Information System (INIS)

Kitaoka, Yoshinori; Kobayashi, Mitsue; Morimoto, Tsuguhiro; Kirihata, Mitsunori; Ichimoto, Itsuo.

1995-01-01

As the boron carriers for boron neutron capture therapy, p-borono phenylalanine (BPA) is the boron compound which has been clinically used together with sodium borocaptate. It was found by the electrophoresis behavior that the BPA interacted with organic carboxylic acids in its dissolved state. In this paper, the electrophoresis behavior of general amino acids as seen in three-spot zone electrophoresis and the peculiar interaction of the amino acids having dihydroxyboryl radical are described. Zone electrophoresis has been developed as separation means, and three-spot process excludes the errors due to accidental factors as far as possible. The behaviors of zone electrophoresis of ordinary neutral amino acids, orthoboric acid and p-BPA are reported. For utilizing the features of boron neutron capture therapy, it is necessary to develop the carrier which is singularly taken into cancer cells. There is not a good method for discriminating normal cells and cancer cells. As for the administration of BPA to patients, its solubility is insufficient, therefore, its fructose complex has been used. The research on the biochemical peculiarity of boron is important. (K.I.)

Monte Carlo treatment planning and high-resolution alpha-track autoradiography for neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Zamenhof, R.G.; Lin, K.; Ziegelmiller, D.; Clement, S.; Lui, C.; Harling, O.K.

Monte Carlo simulations of thermal neutron flux distributions in a mathematical head model have been compared to experimental measurements in a corresponding anthropomorphic gelatin-based head phantom irradiated by a thermal neutron beam as presently available at the MITR-II Research Reactor. Excellent agreement between Monte Carlo and experimental measurements has encouraged us to employ the Monte Carlo simulation technique to approach treatment planning problems in neutron capture therapy. We have also implemented a high-resolution alpha-track autoradiography technique originally developed in our laboratory at MIT. Initial autoradiograms produced by this technique meet our expectations in terms of the high resolution available and the ability to etch tracks without concommitant destruction of stained tissue. Our preliminary results with computer-aided track distribution analysis indicate that this approach is very promising in being able to quantify boron distributions in tissue at the subcellular level with a minimum amount of operator effort necessary.

Establishment of optimal thermal neutron capture therapy for 5 types of human malignant melanoma

International Nuclear Information System (INIS)

Mishima, Yutaka

1993-03-01

A series of boron neutron capture therapy (BNCT) studies has already germinated in 1972, with a view to establishing the BNCT particularly suited for the treatment of various types of malignant melanoma, and has been succeeded by research teams comprised of multi-disciplinary members. Twelve patients (7 men and 5 women, aged from 50 to 85 years) with malignant melanoma have been treated with BNCT; among them, six patients were completely cured, four had extremely reduced tumors, and two were still in the clinical process. The present Progress Report is a compilation of 39 research presentations for the recent two years. In this report, three patients are described. Of these, one patient had deep-seated lesions in right and left lymph nodes. These lesions were cured by the use of D 2 O that allowed neutron beams to reach them. Application of positron emission tomography to the diagnosis of melanoma is a highlight in this Report. (N.K.)

Selective uptake of p-boronophenylalanine by osteosarcoma cells for boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Ferrari, C. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)], E-mail: ferraric@unipv.it; Zonta, C.; Cansolino, L.; Clerici, A.M.; Gaspari, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy); Altieri, S.; Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi, 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics of University, Via Bassi, 6, Pavia (Italy); Dionigi, P.; Zonta, A. [Department of Surgery, Experimental Surgery Laboratory, University of Pavia, Piazza Botta, Pavia (Italy)

2009-07-15

Osteosarcoma is the most common non-hematologic primary cancer type that develops in bone. Current osteosarcoma treatments combine multiagent chemotherapy with extensive surgical resection, which in some cases makes necessary the amputation of the entire limb. Nevertheless its infiltrative growth leads to a high incidence of local and distant recurrences that reduce the percentage of cured patients to less than 60%. These poor data required to set up a new therapeutic approach aimed to restrict the surgical removal meanwhile performing a radical treatment. Boron neutron capture therapy (BNCT), a particular radiotherapy based on the nuclear capture and fission reactions by atoms of {sup 10}B, when irradiated with thermal neutrons, could be a valid alternative or integrative option in case of osteosarcoma management, thanks to its peculiarity in selectively destroying neoplastic cells without damaging normal tissues. Aim of the present work is to investigate the feasibility of employing BNCT to treat the limb osteosarcoma. Boronophenylalanine (BPA) is used to carry {sup 10}B inside the neoplastic cells. As a first step the endocellular BPA uptake is tested in vitro on the UMR-106 osteosarcoma cell line. The results show an adequate accumulation capability. For the in vivo experiments, an animal tumor model is developed in Sprague-Dawley rats by means of an intrafemoral injection of UMR-106 cells at the condyle site. The absolute amounts of boron loading and the tumor to normal tissue {sup 10}B ratio are evaluated 2 h after the i.v. administration of BPA. The boron uptake by the neoplastic tissue is almost twice the normal one. However, higher values of boron concentration in tumor are requested before upholding BNCT as a valid therapeutic option in the treatment of osteosarcoma.

GPU-based prompt gamma ray imaging from boron neutron capture therapy

International Nuclear Information System (INIS)

Yoon, Do-Kun; Jung, Joo-Young; Suk Suh, Tae; Jo Hong, Key; Sil Lee, Keum

2015-01-01

Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU). Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusions: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray image reconstruction using the GPU computation for BNCT simulations

Multi-Agent Framework in Visual Sensor Networks

Directory of Open Access Journals (Sweden)

J. M. Molina

2007-01-01

Full Text Available The recent interest in the surveillance of public, military, and commercial scenarios is increasing the need to develop and deploy intelligent and/or automated distributed visual surveillance systems. Many applications based on distributed resources use the so-called software agent technology. In this paper, a multi-agent framework is applied to coordinate videocamera-based surveillance. The ability to coordinate agents improves the global image and task distribution efficiency. In our proposal, a software agent is embedded in each camera and controls the capture parameters. Then coordination is based on the exchange of high-level messages among agents. Agents use an internal symbolic model to interpret the current situation from the messages from all other agents to improve global coordination.

In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma

Energy Technology Data Exchange (ETDEWEB)

Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

2009-01-01

Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.

A standardized method for beam design in neutron capture therapy

International Nuclear Information System (INIS)

Storr, G.J.: Harrington, B.V.

1993-01-01

A desirable end point for a given beam design for Neutron Capture Therapy (NCT) should be quantitative description of tumour control probability and normal tissue damage. Achieving this goal will ultimately rely on data from NCT human clinical trials. Traditional descriptions of beam designs have used a variety of assessment methods to quantify proposed or installed beam designs. These methods include measurement and calculation of open-quotes free fieldclose quotes parameters, such as neutron and gamma flux intensities and energy spectra, and figures-of-merit in tissue equivalent phantoms. The authors propose here a standardized method for beam design in NCT. This method would allow all proposed and existing NCT beam facilities to be compared equally. The traditional approach to determining a quantitative description of tumour control probability and normal tissue damage in NCT research may be described by the following path: Beam design → dosimetry → macroscopic effects → microscopic effects. Methods exist that allow neutron and gamma fluxes and energy dependence to be calculated and measured to good accuracy. By using this information and intermediate dosimetric quantities such as kerma factors for neutrons and gammas, macroscopic effect (absorbed dose) in geometries of tissue or tissue-equivalent materials can be calculated. After this stage, for NCT the data begins to become more sparse and in some areas ambiguous. Uncertainties in the Relative Biological Effectiveness (RBE) of some NCT dose components means that beam designs based on assumptions considered valid a few years ago may have to be reassessed. A standard method is therefore useful for comparing different NCT facilities

Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

International Nuclear Information System (INIS)

Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L.; Bergland, R.; Elowitz, E.; Chadha, M.

1994-01-01

The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report

Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

Energy Technology Data Exchange (ETDEWEB)

Coderre, J.A.; Chanana, A.D.; Joel, D.D.; Liu, H.B.; Slatkin, D.N.; Wielopolski, L. [Brookhaven National Lab., Upton, NY (United States); Bergland, R.; Elowitz, E. [Beth Israel Medical Center, New York, NY (United States). Dept. of Neurosurgery; Chadha, M. [Beth Israel Medical Center, New York, NY (United States). Dept. of Radiation Oncology

1994-12-31

The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report.

In-phantom dosimetry using the 13C(d,n)14N reaction for BNCT (boron neutron capture therapy)

International Nuclear Information System (INIS)

Burlon, Alejandro; Kreiner, Andres J.; White, S.; Blackburn, B.; Gierga, David; Yanch, Jacquelyn C.

2000-01-01

The use of the 13 C(d,n) 14 N reaction at E d =1.5 MeV for accelerator-based boron neutron capture therapy is investigated. The 13 C(d,n) 14 N reaction presents the advantages of carbon as a target material and its large cross section. The deuteron beam was produced by a tandem accelerator at MIT's Laboratory for Accelerator Beam Applications. The resulting neutron spectra were evaluated in terms of RBE-dose rates at different depths inside a water-filled brain phantom using a heavy water moderator and lead reflector assembly. All results were simulated using the code MCNP. (author)

Hadron Therapy: Past, Present and Perspectives

International Nuclear Information System (INIS)

Jones, D.T.L

1999-01-01

Fast neutron therapy began as long ago as 1938 and subsequently proton, alpha particle, heavy ion, pion and neutron capture therapy have been used. To date it is estimated that in excess of 45000 people have undergone some form of hadron therapy. In the future it is expected that fast neutron therapy will be used for selected tumour types for which neutron are known to show improved cure rates. The future trends in charged particle therapy will be driven by increasing commercialization. The future of neutron capture therapy will depend on current clinical trials with epithermal neutron beams and the development of new tumour-seeking drugs

Investigation on the neutron beam characteristics for boron neutron capture therapy with 3D and 2D transport calculations

International Nuclear Information System (INIS)

Kodeli, I.; Diop, C.M.; Nimal, J.C.

1994-01-01

In the framework of future Boron Neutron Capture Therapy (BNCT) experiments, where cells and animals irradiations are planned at the research reactor of Strasbourg University, the feasibility to obtain a suitable epithermal neutron beam is investigated. The neutron fluence and spectra calculations in the reactor are performed using the 3D Monte Carlo code TRIPOLI-3 and the 2D SN code TWODANT. The preliminary analysis of Al 2 O 3 and Al-Al 2 O 3 filters configurations are carried out in an attempt to optimize the flux characteristics in the beam tube facility. 7 figs., 7 refs

Immunological effects of hypomethylating agents.

Science.gov (United States)

Lindblad, Katherine E; Goswami, Meghali; Hourigan, Christopher S; Oetjen, Karolyn A

2017-08-01

Epigenetic changes resulting from aberrant methylation patterns are a recurrent observation in hematologic malignancies. Hypomethylating agents have a well-established role in the management of patients with high-risk myelodysplastic syndrome or acute myeloid leukemia. In addition to the direct effects of hypomethylating agents on cancer cells, there are several lines of evidence indicating a role for immune-mediated anti-tumor benefits from hypomethylating therapy. Areas covered: We reviewed the clinical and basic science literature for the effects of hypomethylating agents, including the most commonly utilized therapeutics azacitidine and decitabine, on immune cell subsets. We summarized the effects of hypomethylating agents on the frequency and function of natural killer cells, T cells, and dendritic cells. In particular, we highlight the effects of hypomethylating agents on expression of immune checkpoint inhibitors, leukemia-associated antigens, and endogenous retroviral elements. Expert commentary: In vitro and ex vivo studies indicate mixed effects on the function of natural killer, dendritic cells and T cells following treatment with hypomethylating agents. Clinical correlates of immune function have suggested that hypomethylating agents have immunomodulatory functions with the potential to synergize with immune checkpoint therapy for the treatment of hematologic malignancy, and has become an active area of clinical research.

In Defense of Agent-Based Virtue Ethics | Van Zyl | Philosophical ...

African Journals Online (AJOL)

In 'Against agent-based virtue ethics' (2004) Michael Brady rejects agent-based virtue ethics on the grounds that it fails to capture the commonsense distinction between an agent's doing the right thing, and her doing it for the right reason. In his view, the failure to account for this distinction has paradoxical results, making it ...

Primary evaluation of a nickel-chlorophyll derivative as a multimodality agent for tumor imaging and photodynamic therapy

International Nuclear Information System (INIS)

Ozge Er; Fatma Yurt Lambrecht; Kasim Ocakoglu; Cagla Kayabasi; Cumhur Gunduz

2015-01-01

In this study, the biological potential of a nickel chlorophyll derivative (Ni-PH-A) as a multimodal agent for tumor imaging and photodynamic therapy (PDT) was investigated. Optimum conditions of labeling with 131 I were investigated and determined as pH 10 and 1 mg amount of iodogen. Biodistribution results of 131 I labeled Ni-PH-A in female rats indicated that radiolabeled Ni-PH-A maximum uptake in the liver, spleen and ovary was observed at 30 min. Intercellular uptake and PDT efficacy of Ni-PH-A were better in MDAH-2774 (human ovarian endometrioid adenocarcinoma) than in MCF-7 (human breast adenocarcinoma) cells. Ni-PH-A might be a promising multimodal agent for lung, ovary and liver tumor imaging and PDT. (author)

The roles of the Q (q) wave in lead I and QRS frontal axis for diagnosing loss of left ventricular capture during cardiac resynchronization therapy.

Science.gov (United States)

Cao, Yuan-Yuan; Su, Yan-Gang; Bai, Jin; Wang, Wei; Wang, Jing-Feng; Qin, Sheng-Mei; Ge, Jun-Bo

2015-01-01

Loss of left ventricular (LV) capture may lead to deterioration of heart failure in patients with cardiac resynchronization therapy (CRT). Recognition of loss of LV capture in time is important in clinical practice. A total of 422 electrocardiograms were acquired and analyzed from 53 CRT patients at 8 different pacing settings (LV only, right ventricle [RV] only, biventricular [BV] pacing with LV preactivation of 60, 40, 20, and 0 milliseconds and RV preactivation of 20 and 40 milliseconds). A modified Ammann algorithm by adding a third step-presence of Q (q, or QS) wave-to the original 2-step Ammann algorithm and a QRS axis shift method were devised to identify the loss of LV capture. The accuracy of modified Ammann algorithm was significantly higher than that of Ammann algorithm (78.9% vs. 69.1%, P capture. The LV preactivation, or simultaneous BV activation and LV lead positioned in nonposterior or noninferior wall can increase the diagnostic power of the modified Ammann algorithm and QRS axis shift method. © 2014 Wiley Periodicals, Inc.

Boron-containing thioureas for neutron capture therapy. Borhaltige Thioharnstoffe fuer die Neutroneneinfangtherapie

Energy Technology Data Exchange (ETDEWEB)

Ketz, H.

1993-10-21

Melanin is produced in large amounts in malignant melanotic melanomas. Because thiourea compounds are covalently incorporated into melanin during its biosynthesis, the preparation of boronated thiourea-derivatives is of particular interest for the BNCT (Boron Neutron Capture Therapy). Accumulation of boron in tumors by means of boronated thiourea-derivatives may therefore provide levels of [sup 10]B which are useful for BNCT. In BNCT the tumor containing the boron compound is irradiated with epithermal neutrons to generate He- and Li-nuclei from the [sup 10]B which can then destroy the tumor cells. Because of the short ranges of these particles (approximately one cell diameter) the damage will be almost exclusively confined to the tumor leaving normal tissue unharmed. High accumulation of 2-mercapto-1-methylimidazole (methimazole) in melanotic melanomas has been described in the literature. Boronated derivatives of methimazole were therefore synthesized. Boron was in the form of a boronic acid, a nido-carbonate and a mercaptoundeca hydro-closo-dodecaborate (BSH). The synthesis of the boron cluster derivatives of methimazole (nido-carborate- and BSH-derivatives) with 9 resp. 12 boron atoms in the molecule were expected to achieve higher concentrations of boron in the tumor than in the case of the boronic acid compound with its single boron atom. (orig.)

PEMODELAN KOLIMATOR DI RADIAL BEAM PORT REAKTOR KARTINI UNTUK BORON NEUTRON CAPTURE THERAPY

Directory of Open Access Journals (Sweden)

Bemby Yulio Vallenry

2015-03-01

Full Text Available Salah satu metode terapi kanker adalah Boron Neutron Capture Therapy (BNCT. BNCT memanfaatkan tangkapan neutron oleh 10B yang terendapkan pada sel kanker. Keunggulan BNCT dibandingkan dengan terapi radiasi lainnya adalah tingkat selektivitas yang tinggi karena tingkatannya adalah sel. Pada penelitian ini dilakukan pemodelan kolimator di radial beamport reaktor Kartini sebagai dasar pemilihan material dan manufature kolimator sebagai sumber neutron untuk BNCT. Pemodelan ini dilakukan dengan simulasi menggunakan perangkat lunak Monte Carlo N-Particle versi 5 (MCNP 5. MCNP 5 adalah suatu paket program untuk memodelkan sekaligus menghitung masalah transpor partikel dengan mengikuti sejarah hidup neutron semenjak lahir, bertranspor pada bahan hingga akhirnya hilang karena mengalami reaksi penyerapan atau keluar dari sistem. Pemodelan ini menggunakan variasi material dan ukurannya agar menghasilkan nilai dari tiap parameter-parameter yang sesuai dengan rekomendasi I International Atomic Energy Agency (IAEA untuk BNCT, yaitu fluks neutron epitermal (Фepi > 9 n.cm-2.s-1, rasio antara laju dosis neutron cepat dan fluks neutron epitermal (Ḋf/Фepi 0,7. Berdasarkan hasil optimasi dari pemodelan ini, material dan ukuran penyusun kolimator yang didapatkan yaitu 0,75 cm Ni sebagai dinding kolimator, 22 cm Al sebagai moderator dan 4,5 cm Bi sebagai perisai gamma. Keluaran berkas radiasi yang dihasilkan dari pemodelan kolimator radial beamport yaitu Фepi = 5,25 x 106 n.cm-2s-1, Ḋf/Фepi =1,17 x 10-13 Gy.cm2.n-1, Ḋγ/Фepi = 1,70 x 10-12 Gy.cm2.n-1, Фth/Фepi = 1,51 dan J/Фepi = 0,731. Berdasarkan penelitian ini, hasil optimasi 5 parameter sebagai persyaratan kolimator untuk BNCT yang keluar dari radial beam port tidak sepenuhnya memenuhi kriteria yang direkomendasikan oleh IAEA sehingga perlu dilakukan penelitian lebih lanjut agar tercapainya persyaratan IAEA. Kata kunci: BNCT, radial beamport, MCNP 5, kolimator   One of the cancer therapy methods is

Agent Communications using Distributed Metaobjects

Energy Technology Data Exchange (ETDEWEB)

Goldsmith, Steven Y.; Spires, Shannon V.

1999-06-10

There are currently two proposed standards for agent communication languages, namely, KQML (Finin, Lobrou, and Mayfield 1994) and the FIPA ACL. Neither standard has yet achieved primacy, and neither has been evaluated extensively in an open environment such as the Internet. It seems prudent therefore to design a general-purpose agent communications facility for new agent architectures that is flexible yet provides an architecture that accepts many different specializations. In this paper we exhibit the salient features of an agent communications architecture based on distributed metaobjects. This architecture captures design commitments at a metaobject level, leaving the base-level design and implementation up to the agent developer. The scope of the metamodel is broad enough to accommodate many different communication protocols, interaction protocols, and knowledge sharing regimes through extensions to the metaobject framework. We conclude that with a powerful distributed object substrate that supports metaobject communications, a general framework can be developed that will effectively enable different approaches to agent communications in the same agent system. We have implemented a KQML-based communications protocol and have several special-purpose interaction protocols under development.

Basic and clinical study of boron neutron capture therapy for malignant brain tumor

International Nuclear Information System (INIS)

Nose, Tadao; Matsumura, Akira; Nakai, Kei; Nakagawa, Kunio; Yoshii, Yoshihiko; Shibata, Yasushi; Yamamoto, Tetsuya; Hayakawa, Yoshinori; Yamada, Takashi

1998-01-01

Rat malignant cells (9L glioma cell) were exposed to neutron radiation after culturing with boron compounds; BSH and STA-BX909, and cell growing ability after the exposure was determined by colony forming assay. The effects of in vivo radiation were examined by measuring neutron flux levels in rat brain and skin aiming to use neutron radiation in clinical study. STA-BX909 was found to show a dose-dependent cell toxicity, which was higher than that of BSH. The radiation induced G2/M block in 9L-glioma cells and their cell cycles recovered thereafter in low-dose radiated cells, but high-dose radiated cells became aneuploidy. Furthermore, boron neutron capture therapy (BNCT) was applied in two patients, 41-year old woman with glioma grade 3 recurred and 45-year old man with glioblastoma multiforme. The former died from systemic deterioration due to ileus, but BNCT was made only one time although conventional radiotherapy is carried out for a relatively long period. Therefore, BNCT was thought to be beneficial from an aspect of 'quality of life' and the effects to repress a recurrence of cancer also seemed larger than the conventional one. (M.N.)

Basic and clinical study of boron neutron capture therapy for malignant brain tumor

Energy Technology Data Exchange (ETDEWEB)

Nose, Tadao; Matsumura, Akira; Nakai, Kei; Nakagawa, Kunio; Yoshii, Yoshihiko [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Shibata, Yasushi; Yamamoto, Tetsuya; Hayakawa, Yoshinori; Yamada, Takashi

1998-01-01

Rat malignant cells (9L glioma cell) were exposed to neutron radiation after culturing with boron compounds; BSH and STA-BX909, and cell growing ability after the exposure was determined by colony forming assay. The effects of in vivo radiation were examined by measuring neutron flux levels in rat brain and skin aiming to use neutron radiation in clinical study. STA-BX909 was found to show a dose-dependent cell toxicity, which was higher than that of BSH. The radiation induced G2/M block in 9L-glioma cells and their cell cycles recovered thereafter in low-dose radiated cells, but high-dose radiated cells became aneuploidy. Furthermore, boron neutron capture therapy (BNCT) was applied in two patients, 41-year old woman with glioma grade 3 recurred and 45-year old man with glioblastoma multiforme. The former died from systemic deterioration due to ileus, but BNCT was made only one time although conventional radiotherapy is carried out for a relatively long period. Therefore, BNCT was thought to be beneficial from an aspect of `quality of life` and the effects to repress a recurrence of cancer also seemed larger than the conventional one. (M.N.)

Research of accelerator-based neutron source for boron neutron capture therapy

International Nuclear Information System (INIS)

Li Changkai; Ma Yingjie; Tang Xiaobin; Xie Qin; Geng Changran; Chen Da

2013-01-01

Background: 7 Li (p, n) reaction of high neutron yield and low threshold energy has become one of the most important neutron generating reactions for Accelerator-based Boron Neutron Capture Therapy (BNCT). Purpose Focuses on neutron yield and spectrum characteristics of this kind of neutron generating reaction which serves as an accelerator-based neutron source and moderates the high energy neutron beams to meet BNCT requirements. Methods: The yield and energy spectrum of neutrons generated by accelerator-based 7 Li(p, n) reaction with incident proton energy from 1.9 MeV to 3.0 MeV are researched using the Monte Carlo code-MCNPX2.5.0. And the energy and angular distribution of differential neutron yield by 2.5-MeV incident proton are also given in this part. In the following part, the character of epithermal neutron beam generated by 2.5-MeV incident protons is moderated by a new-designed moderator. Results: Energy spectra of neutrons generated by accelerator-based 7 Li(p, n) reaction with incident proton energy from 1.9 MeV to 3.0 MeV are got through the simulation and calculation. The best moderator thickness is got through comparison. Conclusions: Neutron beam produced by accelerator-based 7 Li(p, n) reaction, with the bombarding beam of 10 mA and the energy of 2.5 MeV, can meet the requirement of BNCT well after being moderated. (authors)

An accelerator-based epithermal photoneutron source for boron neutron capture therapy

International Nuclear Information System (INIS)

Mitchell, H.E.

1996-04-01

Boron neutron capture therapy is an experimental binary cancer radiotherapy modality in which a boronated pharmaceutical that preferentially accumulates in malignant tissue is first administered, followed by exposing the tissue in the treatment volume to a thermal neutron field. Current usable beams are reactor-based but a viable alternative is the production of an epithermal neutron beam from an accelerator. Current literature cites various proposed accelerator-based designs, most of which are based on proton beams with beryllium or lithium targets. This dissertation examines the efficacy of a novel approach to BNCT treatments that incorporates an electron linear accelerator in the production of a photoneutron source. This source may help to resolve some of the present concerns associated with accelerator sources, including that of target cooling. The photoneutron production process is discussed as a possible alternate source of neutrons for eventual BNCT treatments for cancer. A conceptual design to produce epithermal photoneutrons by high photons (due to bremsstrahlung) impinging on deuterium targets is presented along with computational and experimental neutron production data. A clinically acceptable filtered epithermal neutron flux on the order of 10 7 neutrons per second per milliampere of electron current is shown to be obtainable. Additionally, the neutron beam is modified and characterized for BNCT applications by employing two unique moderating materials (an Al/AlF 3 composite and a stacked Al/Teflon design) at various incident electron energies

An accelerator-based epithermal photoneutron source for boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Mitchell, Hannah E. [Georgia Inst. of Technology, Atlanta, GA (United States)

1996-04-01

Boron neutron capture therapy is an experimental binary cancer radiotherapy modality in which a boronated pharmaceutical that preferentially accumulates in malignant tissue is first administered, followed by exposing the tissue in the treatment volume to a thermal neutron field. Current usable beams are reactor-based but a viable alternative is the production of an epithermal neutron beam from an accelerator. Current literature cites various proposed accelerator-based designs, most of which are based on proton beams with beryllium or lithium targets. This dissertation examines the efficacy of a novel approach to BNCT treatments that incorporates an electron linear accelerator in the production of a photoneutron source. This source may help to resolve some of the present concerns associated with accelerator sources, including that of target cooling. The photoneutron production process is discussed as a possible alternate source of neutrons for eventual BNCT treatments for cancer. A conceptual design to produce epithermal photoneutrons by high photons (due to bremsstrahlung) impinging on deuterium targets is presented along with computational and experimental neutron production data. A clinically acceptable filtered epithermal neutron flux on the order of 10⁷ neutrons per second per milliampere of electron current is shown to be obtainable. Additionally, the neutron beam is modified and characterized for BNCT applications by employing two unique moderating materials (an Al/AlF₃ composite and a stacked Al/Teflon design) at various incident electron energies.

Effects of inlet/outlet configurations on the electrostatic capture of airborne nanoparticles and viruses

International Nuclear Information System (INIS)

Jang, Jaesung; Akin, Demir; Bashir, Rashid

2008-01-01

Motivated by capture and detection of airborne biological agents in real time with a cantilever biosensor without introducing the agents into liquids, we present the effects of inlet/outlet configurations of a homemade particle collector on the electrostatic capture of airborne 100 nm diameter nanoparticles under swirling gas flows. This particle collector has three different inlet/outlet configurations: forward inlet/outlet (FO), backward inlet/outlet (BO) and straight inlet/outlet (SO) configurations. We also present the electrostatic capture of Vaccinia viruses using the same particle collector and compare these virus measurements with the nanoparticle cases. The most particles were collected in the FO configuration. The numbers of particles captured in the BO and SO configurations were close within their standard deviations. For all the three configurations tested, the number of particles captured in the center electrode C was much smaller than those captured in the other electrodes at a flow rate of 1.1 l min −1 and an applied potential of 2 kV. Using a commercial CFD code FLUENT, we also simulated the effects of the three inlet/outlet configurations on the particle capture in terms of particle trajectories, velocities and travel times. This simulation was in a good agreement with measurements that the FO configuration is the most favorable to particle capture among the tested configurations at a flow rate of 1.1 l min −1 . The effects of particle diameters on the capture will also be discussed. This collector can be used for real-time monitoring of bioaerosols along with cantilever biosensors

PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

Science.gov (United States)

Vincenzi, Bruno; Santini, Daniele; Schiavon, Gaia; Frezza, Anna Maria; Silletta, Marianna; Crucitti, Pierfilippo; Casali, Paolo; Dei Tos, Angelo P; Rossi, Sabrina; Rizzo, Sergio; Badalamenti, Giuseppe; Tomasino, Rosa Maria; Russo, Antonio; Butrynski, James E; Tonini, Giuseppe

2012-04-01

Soft tissue sarcomas are aggressive tumors representing alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was significantly reduced in synovial sarcomas (P < 0.0001), in myofibroblastic sarcomas (P < 0.0001), angiosarcomas (P < 0.0001), in leiomyosarcomas (P = 0.003), in mixoid liposarcomas (P < 0.0001), and in dedifferentiated liposarcomas (P < 0.0001). No significant difference was found for pleomorphic sarcoma [31.8 (95% CI: 16.7-41.0); P = 0.21]. and pleomorphic liposarcomas (P = 0.51). Loss of PML expression was found to be statistically correlated with TTP (P < 0.0001), median duration of response (P = 0.007), and OS (P = 0.02). No correlation was observed between PML expression and treatment efficacy. PML IHC expression is down-regulated in synovial sarcomas, myofibroblastic sarcomas, angiosarcomas, liposarcoma, and leiomyosarcomas and its expression correlated with prognosis. Copyright © 2011 Wiley Periodicals, Inc.

Accelerator based-boron neutron capture therapy (BNCT)-clinical QA and QC

International Nuclear Information System (INIS)

Suzuki, Minoru; Tanaka, Hiroki; Sakurai, Yoshinori; Yong, Liu; Kashino, Genro; Kinashi, Yuko; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira

2009-01-01

Alpha-particle and recoil Li atom yielded by the reaction ( 10 B, n), due to their high LET properties, efficiently and specifically kill the cancer cell that has incorporated the boron. Efficacy of this boron neutron capture therapy (BNCT) has been demonstrated mainly in the treatment of recurrent head/neck and malignant brain cancers in Kyoto University Research Reactor Institute (KUR). As the clinical trial of BNCT is to start from 2009 based on an accelerator (not on the Reactor), this paper describes the tentative outline of the standard operation procedure of BNCT for its quality assurance (QA) and quality control (QC) along the flow of its clinical practice. Personnel concerned in the practice involve the attending physician, multiple physicians in charge of BNCT, medical physicists, nurses and reactor stuff. The flow order of the actual BNCT is as follows: Pre-therapeutic evaluation mainly including informed consent and confirmation of the prescription; Therapeutic planning including setting of therapy volume, and of irradiation axes followed by meeting for stuffs' agreement, decision of irradiating field in the irradiation room leading to final decision of the axis, CT for the planning, decision of the final therapeutic plan according to Japan Atomic Energy Agency-Computational Dosimetry System (JCDS) and meeting of all related personnel for the final confirmation of therapeutic plan; and BNCT including the transport of patient to KUR, dripping of boronophenylalanine, setting up of the patient on the machine, blood sampling for pharmacokinetics, boron level measurement for decision of irradiating time, switch on/off of the accelerator, confirmation of patient's movement in the irradiated field after the neutron irradiation, blood sampling for confirmation of the boron level, and patient's leave from the room. The QA/QC check is principally to be conducted with the two-person rule. The purpose of the clinical trial is to establish the usefulness of BNCT

Monitoring early tumor response to drug therapy with diffuse optical tomography

Science.gov (United States)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

Results of Study of Sulfur Oxide Reduction During Combustion of Coal-Water Slurry Fuel Through use of Sulfur Capturing Agents

Directory of Open Access Journals (Sweden)

Murko Vasiliy I.

2016-01-01

Full Text Available It is shown that an effective way of burning high sulfur coal is to burn coal-water slurry fuel (CWF prepared on its basis containing a sulfur capture agent (SCA entered in the slurry at the stage of preparation. The technique of thermodynamic analysis of chemical reactions during CWF burning has been developed including burning in the presence of SCA. Using the developed calculation program, the optimal temperature conditions have been determined as required for the effective reduction of sulfur oxides in flue gases when using different types of SCA. According to the results of calculating the composition of CWF combustion products when entering various substances in the burner space as SCA it has been determined that magnesite, calcite, and dolomite are the most effective natural minerals. The analysis of calculated and experimental data proves the efficiency of SCA addition as well as validity of the obtained results.

Experimental and Simulated Characterization of a Beam Shaping Assembly for Accelerator- Based Boron Neutron Capture Therapy (AB-BNCT)

International Nuclear Information System (INIS)

Burlon, Alejandro A.; Valda, Alejandro A.; Girola, Santiago; Minsky, Daniel M.; Kreiner, Andres J.

2010-01-01

In the frame of the construction of a Tandem Electrostatic Quadrupole Accelerator facility devoted to the Accelerator-Based Boron Neutron Capture Therapy, a Beam Shaping Assembly has been characterized by means of Monte-Carlo simulations and measurements. The neutrons were generated via the 7 Li(p, n) 7 Be reaction by irradiating a thick LiF target with a 2.3 MeV proton beam delivered by the TANDAR accelerator at CNEA. The emerging neutron flux was measured by means of activation foils while the beam quality and directionality was evaluated by means of Monte Carlo simulations. The parameters show compliance with those suggested by IAEA. Finally, an improvement adding a beam collimator has been evaluated.

IMPROVED COMPUTATIONAL CHARACTERIZATION OF THE THERMAL NEUTRON SOURCE FOR NEUTRON CAPTURE THERAPY RESEARCH AT THE UNIVERSITY OF MISSOURI

Energy Technology Data Exchange (ETDEWEB)

Stuart R. Slattery; David W. Nigg; John D. Brockman; M. Frederick Hawthorne

2010-05-01

Parameter studies, design calculations and initial neutronic performance measurements have been completed for a new thermal neutron beamline to be used for neutron capture therapy cell and small-animal radiobiology studies at the University of Missouri Research Reactor. The beamline features the use of single-crystal silicon and bismuth sections for neutron filtering and for reduction of incident gamma radiation. The computational models used for the final beam design and performance evaluation are based on coupled discrete-ordinates and Monte Carlo techniques that permit detailed modeling of the neutron transmission properties of the filtering crystals with very few approximations. This is essential for detailed dosimetric studies required for the anticipated research program.

Boron Neutron Capture Therapy activity of diffused tumors at TRIGA Mark II in Pavia

Energy Technology Data Exchange (ETDEWEB)

Bortolussi, S.; Stella, S.; De Bari, A.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy)]|[National Institute of Nuclear Physics (INFN), Pavia (Italy); Bruschi, P.; Bakeine, J.G. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C.; Zonta, A. [Department of Surgery, University of Pavia, Pavia (Italy); Nano, R. [Department of Animal Biology, University of Pavia, Pavia (Italy)

2008-10-29

The Boron neutron Capture Therapy research in Pavia has a long tradition: it begun more than 20 years ago at the TRIGA Mark II reactor of the University. A technique for the treatment of the hepatic metastases was developed, consisting in explanting the liver treated with {sup 10}B, irradiating it in the thermal column of the reactor, and re-implanting the organ in the patient. In the last years, the possibility of applying BNCT to the lung tumours using epithermal collimated neutron beams and without explanting the organ, is being explored. The principal obtained results of the BNCT research will be presented, with particular emphasis on the following aspects: a) the project of a new thermal column configuration to make the thermal neutron flux more uniform inside the explanted liver, b) the Monte Carlo study by means of the MCNP code of the thermal neutron flux distribution inside a patient's thorax irradiated with epithermal neutrons, and c) the measurement of the boron concentration in tissues by (n,{alpha}) spectroscopy and neutron autoradiography. (authors)

Boron Neutron Capture Therapy activity of diffused tumors at TRIGA Mark II in Pavia

International Nuclear Information System (INIS)

Bortolussi, S.; Stella, S.; De Bari, A.; Altieri, S.; Bruschi, P.; Bakeine, J.G.; Clerici, A.; Ferrari, C.; Zonta, C.; Zonta, A.; Nano, R.

2008-01-01

The Boron neutron Capture Therapy research in Pavia has a long tradition: it begun more than 20 years ago at the TRIGA Mark II reactor of the University. A technique for the treatment of the hepatic metastases was developed, consisting in explanting the liver treated with 10 B, irradiating it in the thermal column of the reactor, and re-implanting the organ in the patient. In the last years, the possibility of applying BNCT to the lung tumours using epithermal collimated neutron beams and without explanting the organ, is being explored. The principal obtained results of the BNCT research will be presented, with particular emphasis on the following aspects: a) the project of a new thermal column configuration to make the thermal neutron flux more uniform inside the explanted liver, b) the Monte Carlo study by means of the MCNP code of the thermal neutron flux distribution inside a patient's thorax irradiated with epithermal neutrons, and c) the measurement of the boron concentration in tissues by (n,α) spectroscopy and neutron autoradiography. (authors)

Cell cycle dependence of boron uptake in various boron compounds used for neutron capture therapy

International Nuclear Information System (INIS)

Yoshida, F.; Matsumura, A.; Shibata, Y.; Yamamoto, T.; Nose, T.; Okumura, M.

2000-01-01

In neutron capture therapy, it is important that the tumor take boron in selectively. Furthermore, it is ideal when the uptake is equal in each tumor cell. Some indirect proof of differences in boron uptake among neoplastic cell cycles has been documented. However, no investigation has yet measured boron uptake directly. Using flow cytometry, in the present study cells were sorted by G0/G1 phase and G2/M phase, and the boron concentration of each fraction was measured with inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The results were that BSH (sodiumborocaptate) and BPA (p-boronophenylalanine) had higher rates of boron uptake in the G2/M group than in the G0/G1 group. However, in BPA the difference was more prominent, which revealed a 2.2-3.3 times higher uptake of boron in the G2/M group than in the G0/G1 group. (author)

Mn2+-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy

Directory of Open Access Journals (Sweden)

Xi J

2017-04-01

Full Text Available Juqun Xi,1–3 Lanyue Da,1 Changshui Yang,1 Rui Chen,4 Lizeng Gao,2 Lei Fan,5 Jie Han5 1Pharmacology Department, Medical School, Yangzhou University, 2Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, 3Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 4Department of Nephrology, Subei People’s Hospital, Yangzhou University, 5School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China Abstract: Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn2+-coordinated doxorubicin (DOX-loaded poly(lactic-co-glycolic acid (PLGA nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn2+-PDA@DOX/PLGA nanoparticles. In our system, Mn2+-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn2+ could afford the high magnetic resonance (MR imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn2+-PDA@DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties. Keywords: PLGA nanoparticles, polydopamine, chemo-photothermal therapy, smart theranostic agent

Radiation Transport Simulation for Boron Neutron Capture Therapy (BNCT)

Energy Technology Data Exchange (ETDEWEB)

Ziegner, M.; Blaickner, M. [AIT Austrian Institute of Technology GmbH, Health and Environment Department, Molecular Medicine, Muthgasse 11, 1190 Wien (Austria); Ziegner, M.; Khan, R.; Boeck, H. [Vienna University of Technology, Institute of Atomic and Subatomic Physics, Stadionallee 2, 1020 Wien (Austria); Bortolussi, S.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, National Institute of Nuclear Physics (INFN) Pavia Section, Pavia (Italy); Schmitz, T.; Hampel, G. [Nuclear Chemistry, University of Mainz, Fritz Strassmann Weg 2, 55099 Mainz (Germany)

2011-07-01

This work is part of a larger project initiated by the University of Mainz and aiming to use the university's TRIGA reactor to develop a treatment for liver metastases based on Boron Neutron Capture Therapy (BNCT). Diffuse distribution of cancerous cells within the organ makes complete resection difficult and the vicinity to radiosensitive organs impedes external irradiation. Therefore the method of 'autotransplantation', first established at the University of Pavia, is used. The liver is taken out of the body, irradiated in the thermal column of the reactor, therewith purged of metastases and then reimplanted. A highly precise dosimetry system is to be developed by means of measurements at the University of Mainz and computational calculations at the AIT. The stochastic MCNP-5 Monte Carlo-Code, developed by Los Alamos Laboratories, is applied. To verify the calculations of the flux and the absorbed dose in matter a number of measurements are performed irradiating different phantoms and liver sections in a 20cm x 20cm beam tube, which was created by removing graphite blocks from the thermal column of the reactor. The detector material consists of L- {alpha} -alanine pellets which are thought to be the most suitable because of their good tissue equivalence, small size and their wide response range. Another experiment focuses on the determination of the relative biological effectiveness (RBE-factor) of the neutron and photon dose for liver cells. Therefore cell culture plates with the cell medium enriched with {sup 157}Gd and {sup 10}B at different concentrations are irradiated. With regard to the alanine pellets MCNP-5 calculations give stable results. Nevertheless the absorbed dose is underestimated compared to the measurements, a phenomenon already observed in previous works. The cell culture calculations showed the enormous impact of the added isotopes with high thermal neutron cross sections, especially {sup 157}Gd, on the absorbed dose

Measuring the effects of topically applied skin optical clearing agents and modeling the effects and consequences for laser therapies

Science.gov (United States)

Verkruysse, Wim; Khan, Misbah; Choi, Bernard; Svaasand, Lars O.; Nelson, J. Stuart

2005-04-01

Human skin prepared with an optical clearing agent manifests reduced scattering as a result of de-hydration and refractive index matching. This has potentially large effects for laser therapies of several skin lesions such as port wine stain, hair removal and tattoo removal. With most topically applied clearing agents the clearing effect is limited because they penetrate poorly through the intact superficial skin layer (stratum corneum). Agent application modi other than topical are impractical and have limited the success of optical clearing in laser dermatology. In recent reports, however, a mixture of lipofylic and hydrofylic agents was shown to successfully penetrate through the intact stratum corneum layer which has raised new interest in this field. Immediately after application, the optical clearing effect is superficial and, as the agent diffuses through the skin, reduced scattering is manifested in deeper skin layers. For practical purposes as well as to maximize therapeutic success, it is important to quantify the reduced scattering as well as the trans-cutaneous transport dynamics of the agent. We determined the time and tissue depth resolved effects of optically cleared skin by inserting a microscopic reflector array in the skin. Depth dependent light intensity was measured by quantifying the signal of the reflector array with optical coherence tomography. A 1-dimensional mass diffusion model was used to estimate a trans-cutaneous transport diffusion constant for the clearing agent mixture. The results are used in Monte Carlo modeling to determine the optimal time of laser treatment after topical application of the optical clearing agent.

OPTIMIZATION OF THE EPITHERMAL NEUTRON BEAM FOR BORON NEUTRON CAPTURE THERAPY AT THE BROOKHAVEN MEDICAL RESEARCH REACTOR.

Energy Technology Data Exchange (ETDEWEB)

HU,J.P.; RORER,D.C.; RECINIELLO,R.N.; HOLDEN,N.E.

2002-08-18

Clinical trials of Boron Neutron Capture Therapy for patients with malignant brain tumor had been carried out for half a decade, using an epithermal neutron beam at the Brookhaven's Medical Reactor. The decision to permanently close this reactor in 2000 cut short the efforts to implement a new conceptual design to optimize this beam in preparation for use with possible new protocols. Details of the conceptual design to produce a higher intensity, more forward-directed neutron beam with less contamination from gamma rays, fast and thermal neutrons are presented here for their potential applicability to other reactor facilities. Monte Carlo calculations were used to predict the flux and absorbed dose produced by the proposed design. The results were benchmarked by the dose rate and flux measurements taken at the facility then in use.

Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

International Nuclear Information System (INIS)

Andoh, T.; Fujimoto, T.; Sudo, T.; Fujita, I.; Imabori, M.; Moritake, H.; Sugimoto, T.; Sakuma, Y.; Takeuchi, T.; Kawabata, S.; Kirihata, M.; Akisue, T.; Yayama, K.; Kurosaka, M.; Miyatake, S.; Fukumori, Y.; Ichikawa, H.

2011-01-01

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

Energy Technology Data Exchange (ETDEWEB)

Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

2011-12-15

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of {sup 10}B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

Effectiveness of boron neutron capture therapy for recurrent head and neck malignancies

Energy Technology Data Exchange (ETDEWEB)

Kato, Itsuro [Department of Oral and Maxillofacial Surgery, II Osaka University, Graduate School of Dentistry, Osaka (Japan)], E-mail: katoitsu@dent.osaka-u.ac.jp; Fujita, Yusei [Department of Oral and Maxillofacial Surgery, II Osaka University, Graduate School of Dentistry, Osaka (Japan); Maruhashi, Akira [Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka (Japan); Kumada, Hiroaki [Japan Atomic Energy Agency, Tokai Research and Development Center, Ibaraki (Japan); Ohmae, Masatoshi [Department of Oral and Maxillofacial Surgery, Izimisano Municipal Hospital, Rinku General Hospital, Izumisano, Osaka (Japan); Kirihata, Mitsunori [Graduate School of Environment and Life Science, Osaka prefectural University, Osaka (Japan); Imahori, Yoshio [Department of Neurosurgery, Kyoto Prefectural University, Kyoto (Japan); CEO of Cancer Intelligence Care Systems, Inc., Tokyo (Japan); Suzuki, Minoru [Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka (Japan); Sakrai, Yoshinori [Graduate School of Medicine, Sapporo Medical University of Medicine, Hokkaido (Japan); Sumi, Tetsuro; Iwai, Soichi; Nakazawa, Mitsuhiro [Department of Oral and Maxillofacial Surgery, II Osaka University, Graduate School of Dentistry, Osaka (Japan); Murata, Isao; Miyamaru, Hiroyuki [Division of Electrical, Electronic and Information Engineering, Graduate School of Engineering, Osaka University (Japan); Ono, Koji [Radiation Oncology Research Laboratory, Research Reactor Institut, Kyoto University, Osaka (Japan)

2009-07-15

It is necessary to explore new treatments for recurrent head and neck malignancies (HNM) to avoid severe impairment of oro-facial structures and functions. Boron neutron capture therapy (BNCT) is tumor-cell targeted radiotherapy that has significant superiority over conventional radiotherapies in principle. We have treated with BNCT 42 times for 26 patients (19 squamous cell carcinomas (SCC), 4 salivary gland carcinomas and 3 sarcomas) with a recurrent and far advanced HNM since 2001. Results of (1) {sup 10}B concentration of tumor/normal tissue ratios (T/N ratio) of FBPA-PET studies were SCC: 1.8-5.7, sarcoma: 2.5-4.0, parotid tumor: 2.5-3.7. (2) Therapeutic effects were CR: 12 cases, PR: 10 cases, PD: 3 cases NE (not evaluated): 1 case. Response rate was 85%. (3) Improvement of QOL such as a relief of severe pain, bleeding, and exudates at the local lesion, improvement of PS, disappearance of ulceration, covered with normal skin and preserved oral and maxillofacial functions and tissues. (4) Survival periods after BNCT were 1-72 months (mean: 13.6 months). Six-year survival rate was 24% by Kaplan-Meier analysis. (5) Adverse-events were transient mucositis and alopecia in most of the cases; three osteomyelitis and one brain necrosis were recognized. These results indicate that BNCT represents a new and promising treatment approach for advanced HNM.

Intracellular targeting of mercaptoundecahydrododecaborate (BSH) to malignant glioma by transferrin-PEG liposomes for boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Doi, Atsushi; Miyatake, Shin-ichi; Iida, Kyouko

2006-01-01

Malignant glioma is one of the most difficult tumor to control with usual therapies. In our institute, we select boron neutron capture therapy (BNCT) as an adjuvant radiation therapy after surgical resection. This therapy requires the selective delivery of high concentration of 10 B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10 B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10 B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10 B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10 B/ml derived from each BDS by inductively coupled plasma atomic emission spectrometry (ICP-AES). In vivo, human U87Δ glioma-bearing nude mice were administered with each BDS (35mg 10 B/kg) intravenously. We analyzed 10 B concentration of tumor, normal brain and blood by ICP-AES. The TF-PEG liposome-BSH showed higher absolute concentration more than the other BDS. Moreover, TF-PEG liposome-BSH decreased 10 B concentration in blood and normal tissue while it maintained high 10 B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10 B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10 B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

Intraoperative boron neutron capture therapy for malignant gliomas. First clinical results of Tsukuba phase I/II trial using JAERI mixed thermal-epithermal beam

International Nuclear Information System (INIS)

Matsumura, A.; Yamamoto, T.; Shibata, Y.

2000-01-01

Since October 1999, a clinical trial of intraoperative boron neutron capture therapy (IOBNCT) is in progress at JRR-4 (Japan Research Reactor-4) in Japan Atomic Energy Research Institute (JAERI) using mixed thermal-epithermal beam (thermal neutron beam I: TNB-I). Compared to pure thermal beam (thermal neutron beam II: TNB-II), TNB-I has an improved neutron delivery into the deep region than TNB-II. The clinical protocol and the preliminary results will be discussed. (author)

Enhanced therapeutic effect on murine melanoma and angiosarcoma cells by boron neutron capture therapy using a boronated metalloporphyrin

International Nuclear Information System (INIS)

Yamada, Yoshihiko; Ichihashi, Masamitsu; Kahl, S.B.; Toda, Ken-ichi.

1994-01-01

We have already achieved successful treatment of several human patients with malignant melanoma by boron neutron capture therapy (BNCT) using 10 B 1 -paraboronophenylalanine ( 10 B 1 -BPA·HCl). In this study we used a new compound, a manganese boronated protoporphyrin (Mn- 10 BOPP), and compared it to 10 B 1 -BPA·HCl with respect to uptake in murine melanoma and angiosarcoma cells as well as to their cell killing effect. 10 B uptake was measured in a new method, and the new compound was much more incorporated into both cells than 10 B 1 -BPA·HCl. Furthermore, melanoma and angiosarcoma cells preincubated with the new compound were 15 to 20 times more efficiently killed by BNCT than cells preincubated with 10 B 1 -BPA·HCl. (author)

ETUDE FONCTIONNELLE DES SYSTEMES DE CAPTURE SYNAPTOSOMALE ET VESICULAIRE DE DOPAMINE

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M SLIMANI

2001-06-01

Full Text Available L‘injection stéréotaxique unilatérale dans la substance noire de la 6 hydroxy-dopamine ( 6OH-DA se traduit par une chute  parallèle  de  la   capture de dopamine tritiée au  niveau  synaptosomale de  l'ordre  de -70 % et dans les préparations vésiculaires de l'ordre de -69 %, comparées aux préparations issues de Rats non lésés. Ces résultats montrent que ces deux préparations synaptosomales et vésiculaires sont bien d'origine dopaminergique. D'autre part, une étude comparative de l'effet de quelques agents pharmacologiques (β carbolines, imipraminiques, amphétamine et les inhibiteurs purs de la capture synaptosomale sur la capture synaptosomale et vésiculaire de la dopamine tritiée in-vitro, montre qu'ils agissent comme de puissants inhibiteurs. Nous montrons également que le transporteur vésiculaire diffère du transporteur synaptosomal par sa stéréospécificité et sa sensibilité aux agents pharmacologiques.

Beam neutron energy optimization for boron neutron capture therapy using monte Carlo method

International Nuclear Information System (INIS)

Pazirandeh, A.; Shekarian, E.

2006-01-01

In last two decades the optimal neutron energy for the treatment of deep seated tumors in boron neutron capture therapy in view of neutron physics and chemical compounds of boron carrier has been under thorough study. Although neutron absorption cross section of boron is high (3836b), the treatment of deep seated tumors such as glioblastoma multiform requires beam of neutrons of higher energy that can penetrate deeply into the brain and thermalized in the proximity of the tumor. Dosage from recoil proton associated with fast neutrons however poses some constraints on maximum neutron energy that can be used in the treatment. For this reason neutrons in the epithermal energy range of 10eV-10keV are generally to be the most appropriate. The simulation carried out by Monte Carlo methods using MCBNCT and MCNP4C codes along with the cross section library in 290 groups extracted from ENDF/B6 main library. The ptimal neutron energy for deep seated tumors depends on the sue and depth of tumor. Our estimated optimized energy for the tumor of 5cm wide and 1-2cm thick stands at 5cm depth is in the range of 3-5keV

Bead Capture and Release on a Magnetic Sensor in a Microfluidic System

DEFF Research Database (Denmark)

Dalslet, Bjarke Thomas; Damsgaard, Christian Danvad; Freitas, S.C.

Planar Hall effect magnetic sensors for detection of biological agents using surface treated magnetic beads are integrated with a fluid injection system. The response of the sensors is used to evaluate bead capture rates for different bead concentrations c and fluid flow rates Q, and to monitor...... subsequent removal of the beads. It is found that the capture rate scales directly with c and that it depends linearly on Q. At low Q the capture rate is only partially due to gravitational sedimentation of beads. At higher Q an additional term proportional to Q becomes important, which is attributed...... to capture of beads by the magnetic fields near the sensor. It is shown that beads can be washed off the sensor surface....

New antithrombotic agents in the ambulatory setting.

Science.gov (United States)

Gibbs, Neville M; Weightman, William M; Watts, Stephen A

2014-12-01

Many patients presenting for surgical or other procedures in an ambulatory setting are taking new antiplatelet or anticoagulant agents. This review assesses how the novel features of these new agents affect the management of antithrombotic therapy in the ambulatory setting. There have been very few studies investigating the relative risks of continuing or ceasing new antithrombotic agents. Recent reviews indicate that the new antithrombotic agents offer greater efficacy or ease of administration but are more difficult to monitor or reverse. They emphasize the importance of assessing the bleeding risk of the procedure, the thrombotic risk if the agent is ceased, and patient factors that increase the likelihood of bleeding. The timing of cessation of the agent, if required, depends on its pharmacokinetics and patients' bleeding risks. Patients at high risk of thrombotic complications may require bridging therapy. Once agreed upon, the perioperative plan should be made clear to all involved. As there are few clinical studies to guide management, clinicians must make rational decisions in relation to continuing or ceasing new antithrombotic agents. This requires knowledge of their pharmacokinetics, and a careful multidisciplinary assessment of the relative thrombotic and bleeding risks in individual patients.

The potential for tumor suppressor gene therapy in head and neck cancer.

Science.gov (United States)

Birkeland, Andrew C; Ludwig, Megan L; Spector, Matthew E; Brenner, J Chad

2016-01-01

Head and neck squamous cell carcinoma remains a highly morbid and fatal disease. Importantly, genomic sequencing of head and neck cancers has identified frequent mutations in tumor suppressor genes. While targeted therapeutics increasingly are being investigated in head and neck cancer, the majority of these agents are against overactive/overexpressed oncogenes. Therapy to restore lost tumor suppressor gene function remains a key and under-addressed niche in trials for head and neck cancer. Recent advances in gene editing have captured the interest of both the scientific community and the public. As our technology for gene editing and gene expression modulation improves, addressing lost tumor suppressor gene function in head and neck cancers is becoming a reality. This review will summarize new techniques, challenges to implementation, future directions, and ethical ramifications of gene therapy in head and neck cancer.

About neutron capture therapy method development at WWR-SM reactor in institute of Nuclear Physics of Uzbekistan Academy of Sciences

International Nuclear Information System (INIS)

Abdullaeva, G.A.; Baytelesov, S.A.; Dosimbaev, A.A.; Koblik, Yu.N.; Gritsay, O.O.

2006-01-01

Full text: Neutron capture therapy (NCT) is developing method of swellings treatment, on which specialists set one's serious hopes, as at its realization the practical possibilities of the effect on any swellings open. The essence of method is simple and lies in the fact that to the swelling enter preparation containing boron or gadolinium, which one have a large capture cross-section of the thermal and slow neutrons. Then the swelling is irradiated once with the slow (epithermal) neutron beam with fluency about 10 9 neutrons /sm 2 s for a short time and single. As a result of thermal neutrons capture by the boron (or gadolinium) nuclei secondary radiation which affecting swelling cells is emitted. NCT of oncologic diseases makes the specific demands to physical parameters of neutron beams. Now research reactors are often used for NCT. However, research reactor WWR-SM (INP, Uzbekistan AS, Tashkent) doesn't provide with the epithermal neutron beams and to develop this technique the reactor, first of all, needs for obtaining the epithermal neutron beams with energy spectrum in range from 1 eV up to 10 keV and with intensity ∼ 10 9 neutron /sm 2 s. Practically it is connected with upgrade of at least one of existed reactor channels, namely with equipping with the special equipment (filters), forming from the reactor spectrum the beam of necessary energy neutrons. It requires realization of preliminary model calculations, including calculations of capture cross-sections, of filters types and their geometrical parameters on the basis of optimal selected materials. Such calculations, as a rule, are carried out on the basis of Monte-Carlo method and designed software for calculation of nuclear reactor physical and technical characteristics [1]. In this work the calculation results of devices variants and problems discussion, related with possibility of WWR-SM reactor using for NCT are presented. (author)

Induction immunosuppressive therapies in renal transplantation.

Science.gov (United States)

Gabardi, Steven; Martin, Spencer T; Roberts, Keri L; Grafals, Monica

2011-02-01

Induction immunosuppressive therapies for patients undergoing renal transplantation are reviewed. The goal of induction therapy is to prevent acute rejection during the early posttransplantation period by providing a high degree of immunosuppression at the time of transplantation. Induction therapy is often considered essential to optimize outcomes, particularly in patients at high risk for poor short-term outcomes. All of the induction immunosuppressive agents currently used are biological agents and are either monoclonal (muromonab-CD3, daclizumab, basiliximab, alemtuzumab) or polyclonal (antithymocyte globulin [equine] or antithymocyte globulin [rabbit]) antibodies. Although antithymocyte globulin (rabbit) is not labeled for induction therapy, it is used for this purpose more than any other agent. Basiliximab is not considered as potent an immunosuppressive agent but has a much more favorable adverse-effect profile compared with antithymocyte globulin (rabbit) and is most commonly used in patients at low risk for acute rejection. Rituximab is being studied for use as induction therapy but to date has not demonstrated any significant benefits over placebo. While head-to-head data are available comparing most induction agents, the final decision on the most appropriate induction therapy for a transplant recipient is highly dependent on preexisting medical conditions, donor characteristics, and the maintenance immunosuppressive regimen to be used. No standard induction immunosuppressive regimen exists for patients undergoing renal transplantation. Antithymocyte globulin (rabbit) is the most commonly used agent, whereas basiliximab appears safer. The choice of regimen depends on the preferences of clinicians and institutions.

New anabolic therapies in osteoporosis.

Science.gov (United States)

Rubin, Mishaela R; Bilezikian, John P

2003-03-01

Anabolic agents represent an important new advance in the therapy of osteoporosis. Their potential might be substantially greater than the anti-resorptives. Because the anti-resorptives and anabolic agents work by completely distinct mechanisms of action, it is possible that the combination of agents could be significantly more potent than either agent alone. Recent evidence suggests that a plateau in BMD might occur after prolonged exposure to PTH. Anti-resorptive therapy during or after anabolic therapy might prevent this skeletal adaptation. Protocols to consider anabolic agents as intermittent recycling therapy would be of interest. Of all the anabolics, PTH is the most promising. However, there are unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. More large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Rising expectations that anabolic therapies for osteoporosis will soon play a major role in treating this disease are likely to fuel further studies and the development of even more novel approaches to therapy.

Cystatin capture elisa immunodiagnosis of human fasciolosis at Chupaca-Junin Province

International Nuclear Information System (INIS)

Cornejo, W.; Alva, P.; Sevilla, C.; Huiza, A.; Universidad Nacional Mayor de San Marcos, Lima

2003-01-01

To determine the prevalence of human fasciolosis in an endemic area by means of an Enzyme-Linked Immunosorbent Assay (ELISA) using cystatin as a capture agent for the detection of specific antibodies to fasciola hepatica cysteine proteinases. An ELISA plate was sensitized with cystatin, incubated with excretory-secretory products of adult flukes, and followed by standard ELISA procedures. Clinical applicability of the cystatin capture ELISA for the immunodiagnosis of fasciolosis was tested with 200 serum samples of children and adults from an endemic area in Chupaca province, Junin department. Serum samples from the endemic area tested by cystatin capture ELISA showed 27/200 (13,5%) of positive cases. Fasciolosis remains a major health problem at Chupaca province, Junin department

Verification of the computational dosimetry system in JAERI (JCDS) for boron neutron capture therapy

International Nuclear Information System (INIS)

Kumada, H; Yamamoto, K; Matsumura, A; Yamamoto, T; Nakagawa, Y; Nakai, K; Kageji, T

2004-01-01

Clinical trials for boron neutron capture therapy (BNCT) by using the medical irradiation facility installed in Japan Research Reactor No. 4 (JRR-4) at Japan Atomic Energy Research Institute (JAERI) have been performed since 1999. To carry out the BNCT procedure based on proper treatment planning and its precise implementation, the JAERI computational dosimetry system (JCDS) which is applicable to dose planning has been developed in JAERI. The aim of this study was to verify the performance of JCDS. The experimental data with a cylindrical water phantom were compared with the calculation results using JCDS. Data of measurements obtained from IOBNCT cases at JRR-4 were also compared with retrospective evaluation data with JCDS. In comparison with phantom experiments, the calculations and the measurements for thermal neutron flux and gamma-ray dose were in a good agreement, except at the surface of the phantom. Against the measurements of clinical cases, the discrepancy of JCDS's calculations was approximately 10%. These basic and clinical verifications demonstrated that JCDS has enough performance for the BNCT dosimetry. Further investigations are recommended for precise dose distribution and faster calculation environment

Biodistribution of nanoparticles of hydrophobic gadopentetic-acid derivative prepared with a planetary ball mill for neutron-capture therapy of cancer

International Nuclear Information System (INIS)

Nabeta, Chika; Ichikawa, Hideki; Fukumori, Yoshinobu

2006-01-01

Nanoparticles of hydrophobic gadopentetic-acid derivatives (Gd-nanoGR) were prepared with a wet ball-milling process for gadolinium neutron-capture therapy. Ball-milling of solid mass of gadopentetic acid distearylamide with soybean lecithin as a dispersant in the presence of water and subsequent sonication at 70degC resulted in the Gd-nanoGR with the particle size of 63 nm. Biodistribution study using melanoma-bearing hamsters demonstrated that the i.v. injection of the Gd-nanoGR made a higher gadolinium accumulation in tumor (109 μg Gd/g wet tumor at 6h after administration), when compared with the gadolinium-loaded micellar-like nanoparticles previously reported. (author)

Decision theory with resource-bounded agents.

Science.gov (United States)

Halpern, Joseph Y; Pass, Rafael; Seeman, Lior

2014-04-01

There have been two major lines of research aimed at capturing resource-bounded players in game theory. The first, initiated by Rubinstein (), charges an agent for doing costly computation; the second, initiated by Neyman (), does not charge for computation, but limits the computation that agents can do, typically by modeling agents as finite automata. We review recent work on applying both approaches in the context of decision theory. For the first approach, we take the objects of choice in a decision problem to be Turing machines, and charge players for the "complexity" of the Turing machine chosen (e.g., its running time). This approach can be used to explain well-known phenomena like first-impression-matters biases (i.e., people tend to put more weight on evidence they hear early on) and belief polarization (two people with different prior beliefs, hearing the same evidence, can end up with diametrically opposed conclusions) as the outcomes of quite rational decisions. For the second approach, we model people as finite automata, and provide a simple algorithm that, on a problem that captures a number of settings of interest, provably performs optimally as the number of states in the automaton increases. Copyright © 2014 Cognitive Science Society, Inc.

Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

Science.gov (United States)

Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

2011-12-01

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma

International Nuclear Information System (INIS)

Tamat, S.R.; Moore, D.E.; Patwardhan, A.; Hersey, P.

1989-01-01

The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a bridge to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC

Synthesis of o-carboranylmethyl ethers of steroids as potential target substrates for boron neutron capture therapy

International Nuclear Information System (INIS)

Schneiderova, L.; Gruener, B.; Strouf, O.; Kimlova, I.

1992-01-01

o-carboranylmethyl ethers of steroids were synthesized by insertion of steroidal 2-propynyloxy derivatives into 6,9-bis(acetonitrile)decarborane. This reaction provided compounds with an estrane and androstane skeleton, potentially useful in boron neutron capture therapy of hormone-sensitive forms of cancer: 17β-o-carboranylmethyl ether of estradiol IXb (yield 14%) and 3β- and 17β-carboranylmethyl ethers of androstenediol Vb and VIIb (yield 12% and 13%, respectively). Jones oxidation gave the carboranyl derivative of androsten-17-one VIb in 75% yield. As shown by a study of insertion of 3β-(2-propynyloxy)cholest-5-ene (IVa), the low yields of the insertion reaction cannot be increased by change in the reaction conditions. The relative binding affinity of compound IXb to the estrogen receptor from rat uterine and human breast tumor cytosol was 3.0 and 0.29%, respectively, of that of estradiol. (author) 2 figs., 2 tabs., 20 refs

General principles of antimicrobial therapy.

Science.gov (United States)

Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

2011-02-01

Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

Towards the Biological Understanding of CTC: Capture Technologies, Definitions and Potential to Create Metastasis

Directory of Open Access Journals (Sweden)

Ana M.C. Barradas

2013-12-01

Full Text Available Circulating Tumor Cells (CTC are rare cells originated from tumors that travel into the blood stream, extravasate to different organs of which only a small fraction will develop into metastasis. The presence of CTC enumerated with the CellSearch system is associated with a relative short survival and their continued presence after the first cycles of therapy indicates a futile therapy in patients with metastatic carcinomas. Detailed characterization of CTC holds the promise to enable the choice of the optimal therapy for the individual patients during the course of the disease. The phenotype, physical and biological properties are however not well understood making it difficult to assess the merit of recent technological advancements to improve upon the capture of CTC or to evaluate their metastatic potential. Here we will discuss the recent advances in the classification of CTC captured by the CellSearch system, the implications of their features and numbers. Latest capture platforms are reviewed and placed in the light of technology improvements needed to detect CTC. Physical properties, phenotype, viability and proliferative potential and means to assess their proliferation and metastatic capacity will be summarized and placed in the context of the latest CTC capture platforms.

A technique to prepare boronated B72.3 monoclonal antibody for boron neutron capture therapy

International Nuclear Information System (INIS)

Ranadive, G.N.; Rosenzweig, H.S.; Epperly, M.W.

1993-01-01

B72.3 monoclonal antibody has been successfully boronated using mercaptoundecahydro-closo-dodecaborate (boron cage compound). The reagent was incorporated by first reacting the lysine residues of the antibody with m-maleimidobenzoyl succinimide ester (MBS), followed by Michael addition to the maleimido group by the mercapto boron cage compound to form a physiologically stable thioether linkage. Boron content of the antibody was determined by atomic absorption spectroscopy. For biodistribution studies, boronated antibody was radioiodinated with iodogen. 125 I-labeled and boronated B72.3 monoclonal antibody demonstrated clear tumor localization when administered via tail vein injections to athymic nude mice bearing LS174-T tumor xenografts. Boronated antibody was calculated to deliver 10 6 boron atoms per tumor cell. Although this falls short of the specific boron content originally proposed as necessary for boron neutron capture therapy (BNCT), recent calculations suggest that far fewer atoms of 10 B per tumor cell would be necessary to effect successful BNCT when the boron is targeted to the tumor cell membrane. (author)

Alanine and TLD coupled detectors for fast neutron dose measurements in neutron capture therapy (NCT)

Energy Technology Data Exchange (ETDEWEB)

Cecilia, A.; Baccaro, S.; Cemmi, A. [ENEA-FIS-ION, Casaccia RC, Via Anguillarese 301, 00060 Santa Maria di Galeria, Rome (Italy); Colli, V.; Gambarini, G. [Dept. of Physics of the Univ., INFN, Via Celoria 16, 20133 Milan (Italy); Rosi, G. [ENEA-FIS-ION, Casaccia RC, Via Anguillarese 301, 00060 Santa Maria di Galeria, Rome (Italy); Scolari, L. [Dept. of Physics of the Univ., INFN, Via Celoria 16, 20133 Milan (Italy)

2004-07-01

A method was investigated to measure gamma and fast neutron doses in phantoms exposed to an epithermal neutron beam designed for neutron capture therapy (NCT). The gamma dose component was measured by TLD-300 [CaF{sub 2}:Tm] and the fast neutron dose, mainly due to elastic scattering with hydrogen nuclei, was measured by alanine dosemeters [CH{sub 3}CH(NH{sub 2})COOH]. The gamma and fast neutron doses deposited in alanine dosemeters are very near to those released in tissue, because of the alanine tissue equivalence. Couples of TLD-300 and alanine dosemeters were irradiated in phantoms positioned in the epithermal column of the Tapiro reactor (ENEA-Casaccia RC). The dosemeter response depends on the linear energy transfer (LET) of radiation, hence the precision and reliability of the fast neutron dose values obtained with the proposed method have been investigated. Results showed that the combination of alanine and TLD detectors is a promising method to separate gamma dose and fast neutron dose in NCT. (authors)

Development of the JAERI computational dosimetry system (JCDS) for boron neutron capture therapy. Cooperative research

CERN Document Server

Kumada, H; Matsumura, A; Nakagawa, Y; Nose, T; Torii, Y; Uchiyama, J; Yamamoto, K; Yamamoto, T

2003-01-01

The Neutron Beam Facility at JRR-4 enables us to carry out boron neutron capture therapy with epithermal neutron beam. In order to make treatment plans for performing the epithermal neutron beam BNCT, it is necessary to estimate radiation doses in a patient's head in advance. The JAERI Computational Dosimetry System (JCDS), which can estimate distributions of radiation doses in a patient's head by simulating in order to support the treatment planning for epithermal neutron beam BNCT, was developed. JCDS is a software that creates a 3-dimentional head model of a patient by using CT and MRI images, and that generates a input data file automatically for calculation of neutron flux and gamma-ray dose distributions in the brain with the Monte Carlo code MCNP, and that displays these dose distributions on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By using CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is...

CO2 Capture and Reuse

International Nuclear Information System (INIS)

Thambimuthu, K.; Gupta, M.; Davison, J.

2003-01-01

CO2 capture and storage including its utilization or reuse presents an opportunity to achieve deep reductions in greenhouse gas emissions from fossil energy use. The development and deployment of this option could significantly assist in meeting a future goal of achieving stabilization of the presently rising atmospheric concentration of greenhouse gases. CO2 capture from process streams is an established concept that has achieved industrial practice. Examples of current applications include the use of primarily, solvent based capture technologies for the recovery of pure CO2 streams for chemical synthesis, for utilization as a food additive, for use as a miscible agent in enhanced oil recovery operations and removal of CO2 as an undesired contaminant from gaseous process streams for the production of fuel gases such as hydrogen and methane. In these applications, the technologies deployed for CO2 capture have focused on gas separation from high purity, high pressure streams and in reducing (or oxygen deficient) environments, where the energy penalties and cost for capture are moderately low. However, application of the same capture technologies for large scale abatement of greenhouse gas emissions from fossil fuel use poses significant challenges in achieving (at comparably low energy penalty and cost) gas separation in large volume, dilute concentration and/or low pressure flue gas streams. This paper will focus on a review of existing commercial methods of CO2 capture and the technology stretch, process integration and energy system pathways needed for their large scale deployment in fossil fueled processes. The assessment of potential capture technologies for the latter purpose will also be based on published literature data that are both 'transparent' and 'systematic' in their evaluation of the overall cost and energy penalties of CO2 capture. In view of the of the fact that many of the existing commercial processes for CO2 capture have seen applications in

A physical and engineering study on the irradiation techniques in neutron capture therapy aiming for wider application

International Nuclear Information System (INIS)

Sakurai, Y.; Ono, K.; Suzuki, M.; Katoh, I.; Miyatake, S.-I.; Yanagie, H.

2003-01-01

The solo-irradiation of thermal neutrons has been applied for brain cancer and malignant melanoma in the boron neutron capture therapy (BNCT) at the medical irradiation facility of Kyoto University Reactor (KUR), from the first clinical trial in 1974. In 1997, after the facility remodeling, the application of the mix-irradiation of thermal and epi-thermal neutrons was started, and the depth dose distribution for brain cancer has been improved in some degree. In 2001, the solo-irradiation of epi-thermal neutrons also started. It is specially mentioned that the application to oral cancers started at the same time. The BNCT clinical trial using epi-thermal neutron irradiation at KUR, amounts to twelve as of March 2003. The seven trials; more than a half of the total trials, are for oral cancers. From this fact, we think that the wider application to the other cancers is required for the future prosperity of BNCT. The cancers applied for BNCT in KUR at the present time, are brain cancer, melanoma and oral cancers, as mentioned above. The cancers, expected to be applied in near future, are liver cancer, pancreas cancer, lung cancer, tongue cancer, breast cancer, etc.. Any cancer is almost incurable by the other therapy including the other radiation therapy. In the wider application of BNCT to these cancers, the dose-distribution control suitable to each cancer and/or each part, is important. The introduction of multi-directional and/or multi-divisional irradiation is also needed. Here, a physical and engineering study using two-dimensional transport calculation and three-dimensional Monte-Carlo simulation for the irradiation techniques in BNCT aiming for wider application is reported

Analysis of metastasis of melanoma-bearing hamsters in thermal neutron capture therapy

International Nuclear Information System (INIS)

Ueda, Masataka; Mishima, Yutaka; Ichihashi, Masamitsu

1985-01-01

Melanoma-bearing hamsters were divided into three groups: the MG I was treated with both 10 B 1 -para-boronophenylalanine.HCl ( 10 B 1 -BPA) and neutron capture therapy (NCT); the MG II was treated with NCT alone; and the control group (MG III). The most satisfactory effect on regression was seen in the MG I. When the opposite site to the transplanted tumor site was exposed to thermal neutrons, no enhanced effect on metastasis was seen. Tumor cells of MG I and MG II were transplanted subcutaneously 24 hr after NCT into normal hamsters (MG It and MG IIt), and their growth and metastasis abilities were examined. MG It cells possessed neither growth nor metastasis ability; while MG IIt cells showed normal growth and metastasis abilities. Lethal effects on tumor cells seemed to occur in the MG I at 24 hr after NCT, suggesting no effects of NCT on the metastasis ability of tumor cells. Metastasis was seen in 2 of 8 animals in the MG III; however, inhibitory effects on tumor cells were the same as those in the other groups MG I and MG II. When the cells were exposed to 100 rad and 300 rad of gamma rays to assess effects of gamma rays during NCT, neither tumor growth nor lung metastasis was affected. When the tumor was excised with 5 mm margin, relapse occurred in a high incidence. There was no difference in lung metastasis between NCT and gamma irradiation. (Namekawa, K.)

Gadolinium as an element for neutron capture therapy

International Nuclear Information System (INIS)

Brugger, R.M.; Liu, H.B.; Laster, B.H.; Gordon, C.R.; Greenberg, D.D.; Warkentien, L.S.

1992-01-01

At BNL, preparations are being made to test in vitro compounds containing Gd and compare their response to the response of GD-DTPA to determine if one or several compounds can be located that enter the cells and enhance the Auger effect. Two similar rotators with positions for cell vials that have been constructed for these tests. The first rotator is made of only paraffin which simulates healthy tissue and provides control curves. The second rotator has 135 ppM of Gd-157 in the paraffin to simulate a Gd loaded tumor. Cells are irradiated in vials in the paraffin rotator and in the Gd-paraffin rotator at the epithermal beam of the Brookhaven Medical Research Reactor (BMRR). This produces an irradiation similar to what a patient would receive In an actual treatment. A combination of irradiations are made with both rotators; with no Gd compound or IdUrd In the cell media, with only Gd compound in the cell media and with both Gd compound and IdUrd in the cell media. The first set shows the effects of gamma rays from the H(n,gamma) reaction and the prompt gamma rays from capture of neutrons by Gd. The second set shows if there is any effect of Gd being in the cell media or inside the cells, i.e., an Auger effect. The third set shows the effect of enhancement by the IdUrd produced by the gamma rays from neutrons captured by either H or Gd. The fourth set combines all of the reactions and enhancements. Preliminary calculations and physical measurements of the doses that the cells will receive In these rotators have been made

Chelation Therapy for Mercury Poisoning

Directory of Open Access Journals (Sweden)

Rong Guan

2009-01-01

Full Text Available Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

Boron-neutron capture therapy for incurable cancer and inoperable brain tumors

International Nuclear Information System (INIS)

Hatanaka, Hiroshi

1993-01-01

Recent advances in cancer diagnosis and treatment have not yet improved the survival rate of patients with cancers of the brain, liver, etc. In these organs, an extirpation of the organ, which can be done for stomach, breast, cervix, lung, etc. is not allowed, and this fact is the cause of poor therapeutic results. Boron-neutron capture therapy (BNCT) utilizes the nuclear reaction which will take place between the boron-10 (loaded in the cancer cells artificially) and the thermal neutrons (delivered by reactors). The secondary radiations, helium and lithium hit the cancer cell itself and cause the death of the cancer cell while sparing the surrounding normal cells. BNCT is now being tried also by Oda of Kyoto University (9 cases) and by Nakagawa of Tokushima University (7 cases). It has been tried by Mishima (Kobe University) on 12 skin melanoma patients, proving satisfactory local control of the melanomas. Mercaptoundecahydrododecaborate (BHS) and boronophenylalanine (BPA) have been tried for brain tumors and for melanoma. For cancers of the liver and abdominal viscerae, antibody to the tumor specific antigen has been considered a good carrier of boron-10. Surgeons Takahashi, Fujii, Fujii, Yanagie, and Sekiguchi and immunologist Nariuchi of Tokyo University have been involved in the research and have obtained encouraging results in animals. Hatanaka has been proving good effect of BNCT upon giant cerebral arteriovenous malformation (AVM) and skull base meningioma. These diseases, although pathologically benign, have posed difficult problems in neurosurgery. It will be exciting good news to the patients. In conclusion, BNCT appears to be a good means to treat difficult lesions in the brain and other organs which defy sophisticated modern therapeutic means. (author)

Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer

International Nuclear Information System (INIS)

Pillai, Maroor Raghavan Ambikalmajan; Nanabala, Raviteja; Joy, Ajith; Sasikumar, Arun; Knapp, Furn F.

2016-01-01

Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-L-aspartyl-L-glutamate (NAAG) substrate to the PSMA molecule. A number of radiolabeled PSMA inhibitors have been described in the literature and labeled with SPECT, PET and therapeutic radionuclides. Clinical studies with these agents have demonstrated the improved potential of PSMA-targeted PET imaging agents to detect metastatic prostate cancer in comparison with conventional imaging technologies. Although many of these agents have been evaluated in humans, by far the most extensive clinical literature has described use of the 68 Ga and 177 Lu agents. This review describes the design and development of these agents, with a focus on the broad clinical introduction of PSMA targeting motifs labeled with 68 Ga for PET-CT imaging and 177 Lu for therapy. In particular, because of availability from the long-lived 68 Ge (T 1/2 = 270 days)/ 68 Ga (T 1/2 = 68 min) generator system and increasing availability of PET-CT, the 68 Ga-labeled PSMA targeted agent is receiving widespread interest and is one of the fastest growing radiopharmaceuticals for PET-CT imaging.

Hydrophilic MoSe2 Nanosheets as Effective Photothermal Therapy Agents and Their Application in Smart Devices.

Science.gov (United States)

Lei, Zhouyue; Zhu, Wencheng; Xu, Shengjie; Ding, Jian; Wan, Jiaxun; Wu, Peiyi

2016-08-17

A facile poly(vinylpyrrolidone) (PVP)-assisted exfoliation method is utilized to simultaneously exfoliate and noncovalently modify MoSe2 nanosheets. The resultant hydrophilic nanosheets are shown to be promising candidates for biocompatible photothermal therapy (PTT) agents, and they could also be encapsulated into a hydrogel matrix for some intelligent devices. This work not only provides novel insights into exfoliation and modification of transition metal dichalcogenide (TMD) nanosheets but also might spark more research into engineering multifunctional TMD-related nanocomposites, which is in favor of further exploiting the attractive properties of these emerging layered two-dimensional (2D) nanomaterials.

Considerations for boron neutron capture therapy studies; Consideracoes sobre o estudo da BNCT (terapia de captura neutronica por boro)

Energy Technology Data Exchange (ETDEWEB)

Faria Gaspar, P de

1994-12-31

Radiotherapy is indispensable as a mean to eradicate deeply or infiltrating tumor tissue that can not be removed surgically. Therefore, it is not selective and may also kill the surrounding health tissue. The principle of BNCT (Boron Neutron Capture Therapy) consist in targeting a tumor selectively with a boron-10 compound. This nuclide has a large capture cross section for thermal neutrons and the nuclear reaction and the delivered energy in locus will selective the tumor. Since its initial proposal in 1963 BNCT has made much progress, however it is not used in a routine treatment. In this work it was approached some complex procedures, as the obtention of selective boron compounds, the adequate set up of neutron beams, the biodistribution, the in vivo and in vitro studies, and also human patients treatments. This work provide fundamentals about BNCT to professional of different areas of knowledge since it comprises multidisciplinary study. It includes appendixes for the ones not related to the field for a better comprehension of the many aspects involved. It is also presented a glossary containing technical and basic aspects involved. It is also presented a glossary containing technical and basic terms referred in the work. (author). 174 refs, 1 fig, 12 apps.

Hadron therapy at the end of the 20th century

International Nuclear Information System (INIS)

Prokes, K.; Lokajicek, M.

1998-01-01

An overview of radiotherapy methods (brachytherapy, external irradiation with X-rays, betatrons, linear accelerators, hadron therapy, neutron capture therapy) is given, including their description and basic ways of application. Improved results can be achieved through precise dosimetry, diagnostic preparation, mathematical 3D modelling, procedure simulation and conformal therapy (adaptation of the radiation field to the shape of the target volume and preparation of compensation filters). The use of accelerated protons or ions also contributes to a substantial improvement. Neutron capture therapy is a promising method; the problem of suitable chemical compounds carrying boron 10, to be captured by the neoplasm tissue, and the problem of a suitable source of thermal neutrons are being addressed. (M.D.)

Optimal perioperative management of antithrombotic agents in patients with chronic subdural hematoma.

Science.gov (United States)

Amano, Toshiyuki; Takahara, Kenta; Maehara, Naoki; Shimogawa, Takafumi; Mukae, Nobutaka; Sayama, Tetsuro; Arihiro, Shoji; Arakawa, Shuji; Morioka, Takato; Haga, Sei

2016-12-01

The use of antithrombotic agents such as anticoagulants and antiplatelet agents is widespread, and the opportunities to treat patients with chronic subdural hematoma (CSDH) under antithrombotic therapy are growing. However, whether antithrombotic therapy contributes to postoperative complications and recurrences of CSDH and how these agents should be managed in the surgical treatment of CSDH remains unclear. We retrospectively analyzed 150 consecutive patients with CSDH who underwent neurosurgical interventions at Kyushu Rosai Hospital from 2011 to 2015 and followed them for more than 3 months. Of the 150 study patients, 44 received antithrombotic therapy. All anticoagulants and 76% of the antiplatelet agents were discontinued before surgical treatment of CSDH and resumed within 1 week except in 4 patients whose treatment was terminated and 7 patients who developed postoperative complications or underwent reoperations before resumption of these agents. Postoperative hemorrhagic complications associated with surgical treatment of CSDH occurred in 8 patients (5.3%), and there was no significant difference in the incidence of these complications between patients with and without antithrombotic therapy (6.8% vs. 4.7%, respectively; p=0.90). Postoperative thromboembolic complications occurred in 5 patients (5.4%), including 4 patients with antithrombotic therapy; these complications developed before resumption of antithrombotic agents in 2 patients. There was a significant difference in the incidence of postoperative thromboembolic complications between patients with and without antithrombotic therapy (9.1% vs. 0.9%, respectively; p=0.04). There were no significant differences in the incidence of radiographic deterioration or reoperation of ipsilateral or contralateral hematomas between patients with and without antithrombotic therapy after surgical treatment of unilateral CSDH. A history of antithrombotic therapy was significantly correlated with the incidence of

Biomedicines—Moving Biologic Agents into Approved Treatment Options

Directory of Open Access Journals (Sweden)

Kenneth Cornetta

2013-03-01

Full Text Available The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and Europe. Bioengineering of new agents capitalizing on microRNA biology, nanoparticle technology, stem cell biology, and an increasing understanding of immunology predict a rich future for product development. [...

Towards boron neutron capture therapy: the formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane.

Science.gov (United States)

Theodoropoulos, Dimitrios; Rova, Aikaterini; Smith, James R; Barbu, Eugen; Calabrese, Gianpiero; Vizirianakis, Ioannis S; Tsibouklis, John; Fatouros, Dimitrios G

2013-11-15

Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

International Nuclear Information System (INIS)

Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xueshun; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

2013-01-01

Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma

Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats

International Nuclear Information System (INIS)

Trivillin, V.A.; Garabalino, M.A.; Colombo, L.L.

2013-01-01

Boron Neutron Capture Therapy (BNCT) in an experimental model of lung metastases in BDIX rats Introduction: Boron Neutron Capture Therapy (BNCT) is based on selective tumor uptake of boron compounds, followed by neutron irradiation. BNCT was proposed for the treatment of unresectable, diffuse lung metastases. The aim of the present study was to perform BNCT studies in an experimental model of lung metastases. Materials and Methods: 3 x 106/0.5 ml colon carcinoma cells (DHD/K12/TRb) were injected iv in syngeneic BDIX rats. Three weeks post-inoculation, rats with diffuse lung metastases were used for in vivo BNCT studies in the RA-3 Nuclear Reactor. Based on previous biodistribution studies and computational dosimetry with Monte Carlo simulation, 2 doses were prescribed, i.e. 4 Gy and 8 Gy minimum absorbed dose to tumor. The animals were assigned to 5 experimental groups (n= 4 to 8) at each dose level: T0 (euthanized pre-treatment), BPA-BNCT, Comb-BNCT (BPA+GB-10), Beam only (background dose) and Sham (same manipulation, no treatment). Boron concentration was measured in a blood sample taken pre-irradiation to verify that the value was in the range established in previous biodistribution studies. The animals were followed clinically for 2 weeks after neutron irradiation and then euthanized to assess the response of tumor and normal lung, macroscopically and histologically. To date we have evaluated the end-point weight of lung (normal lung + metastases) and % lung weight/body weight as an indicator of tumor growth. Results: The statistical analysis (ANOVA) of % lung weight/body weight showed statistically significant differences (p<0.05) between groups T0 (0.79 ± 0.38) and Sham (1.87 ± 0.91). No statistically significant differences were observed between the Beam only groups (at both dose levels) and Sham. Similar and statistically significant tumor control was induced in the groups BPA-BNCT Low dose (LD) (0.56 ± 0.11), BPA-BNCT High dose (HD) (0.80 ± 0.16), Comb

Evaluation of moderator assemblies for use in an accelerator-based neutron source for boron neutron capture therapy

International Nuclear Information System (INIS)

Woollard, J.E.; Blue, T.E.; Gupta, N.; Gahbauer, R.A.

1998-01-01

The neutron fields produced by several moderator assemblies were evaluated using both in-phantom and in-air neutron field assessment parameters. The parameters were used to determine the best moderator assembly, from among those evaluated, for use in the accelerator-based neutron source for boron neutron capture therapy. For a 10-mA proton beam current and the specified treatment parameters, a moderator assembly consisting of a BeO moderator and a Li 2 CO 3 reflector was found to be the best moderator assembly whether the comparison was based on in-phantom or in-air neutron field assessment parameters. However, the parameters were discordant regarding the moderator thickness. The in-phantom neutron field assessment parameters predict 20 cm of BeO as the best moderator thickness, whereas the in-air neutron field assessment parameters predict 25 cm of BeO as the best moderator thickness

Optimal timing of neutron irradiation for boron neutron capture therapy after intravenous infusion of sodium borocaptate in patients with glioblastoma

International Nuclear Information System (INIS)

Kageji, Teruyoshi; Nagahiro, Shinji; Kitamura, Katsushi; Nakagawa, Yoshinobu; Hatanaka, Hiroshi; Haritz, Dietrich; Grochulla, Frank; Haselsberger, Klaus; Gabel, Detlef

2001-01-01

Purpose: A cooperative study in Europe and Japan was conducted to determine the pharmacokinetics and boron uptake of sodium borocaptate (BSH: Na 2 B 12 H 11 SH), which has been introduced clinically as a boron carrier for boron neutron capture therapy in patients with glioblastoma. Methods and Materials: Data from 56 patients with glioblastoma who received BSH intravenous infusion were retrospectively reviewed. The pharmacokinetics were evaluated in 50 patients, and boron uptake was investigated in 47 patients. Patients received BSH doses between 12 and 100 mg/kg of body weight. For the evaluation, the infused boron dose was scaled linearly to 100 mg/kg BSH. Results: In BSH pharmacokinetics, the average value for total body clearance, distribution volume of steady state, and mean residence time was 3.6±1.5 L/h, 223.3±160.7 L, and 68.0±52.5 h, respectively. The average values of the boron concentration in tumor adjusted to 100 mg/kg BSH, the boron concentration in blood adjusted to 100 mg/kg BSH, and the tumor/blood boron concentration ratio were 37.1±35.8 ppm, 35.2±41.8 ppm, and 1.53±1.43, respectively. A good correlation was found between the logarithmic value of T adj and the interval from BSH infusion to tumor tissue sampling. About 12-19 h after infusion, the actual values for T adj and tumor/blood boron concentration ratio were 46.2±36.0 ppm and 1.70±1.06, respectively. The dose ratio between tumor and healthy tissue peaked in the same interval. Conclusion: For boron neutron capture therapy using BSH administered by intravenous infusion, this work confirms that neutron irradiation is optimal around 12-19 h after the infusion is started

High-power liquid-lithium target prototype for accelerator-based boron neutron capture therapy.

Science.gov (United States)

Halfon, S; Paul, M; Arenshtam, A; Berkovits, D; Bisyakoev, M; Eliyahu, I; Feinberg, G; Hazenshprung, N; Kijel, D; Nagler, A; Silverman, I

2011-12-01

A prototype of a compact Liquid-Lithium Target (LiLiT), which will possibly constitute an accelerator-based intense neutron source for Boron Neutron Capture Therapy (BNCT) in hospitals, was built. The LiLiT setup is presently being commissioned at Soreq Nuclear Research Center (SNRC). The liquid-lithium target will produce neutrons through the (7)Li(p,n)(7)Be reaction and it will overcome the major problem of removing the thermal power generated using a high-intensity proton beam (>10 kW), necessary for sufficient neutron flux. In off-line circulation tests, the liquid-lithium loop generated a stable lithium jet at high velocity, on a concave supporting wall; the concept will first be tested using a high-power electron beam impinging on the lithium jet. High intensity proton beam irradiation (1.91-2.5 MeV, 2-4 mA) will take place at Soreq Applied Research Accelerator Facility (SARAF) superconducting linear accelerator currently in construction at SNRC. Radiological risks due to the (7)Be produced in the reaction were studied and will be handled through a proper design, including a cold trap and appropriate shielding. A moderator/reflector assembly is planned according to a Monte Carlo simulation, to create a neutron spectrum and intensity maximally effective to the treatment and to reduce prompt gamma radiation dose risks. Copyright © 2011 Elsevier Ltd. All rights reserved.

Efficacy of ATR inhibitors as single agents in Ewing sarcoma

DEFF Research Database (Denmark)

Nieto-Soler, Maria; Morgado-Palacin, Isabel; Lafarga, Vanesa

2016-01-01

Ewing sarcomas (ES) are pediatric bone tumors that arise from a driver translocation, most frequently EWS/FLI1. Current ES treatment involves DNA damaging agents, yet the basis for the sensitivity to these therapies remains unknown. Oncogene-induced replication stress (RS) is a known source...... efficacy in ES xenografts as single agents. Expression of EWS/FLI1 or EWS/ERG oncogenic translocations sensitizes non-ES cells to ATR inhibitors. Our data shed light onto the sensitivity of ES to genotoxic agents, and identify ATR inhibitors as a potential therapy for Ewing Sarcomas....

Ultra-fast electron capture by electrosterically-stabilized gold nanoparticles.

Science.gov (United States)

Ghandi, Khashayar; Findlater, Alexander D; Mahimwalla, Zahid; MacNeil, Connor S; Awoonor-Williams, Ernest; Zahariev, Federico; Gordon, Mark S

2015-07-21

Ultra-fast pre-solvated electron capture has been observed for aqueous solutions of room-temperature ionic liquid (RTIL) surface-stabilized gold nanoparticles (AuNPs; ∼9 nm). The extraordinarily large inverse temperature dependent rate constants (k(e)∼ 5 × 10(14) M(-1) s(-1)) measured for the capture of electrons in solution suggest electron capture by the AuNP surface that is on the timescale of, and therefore in competition with, electron solvation and electron-cation recombination reactions. The observed electron transfer rates challenge the conventional notion that radiation induced biological damage would be enhanced in the presence of AuNPs. On the contrary, AuNPs stabilized by non-covalently bonded ligands demonstrate the potential to quench radiation-induced electrons, indicating potential applications in fields ranging from radiation therapy to heterogeneous catalysis.

Boron neutron capture therapy (BNCT) as a new approach for clear cell sarcoma (CCS) treatment: Trial using a lung metastasis model of CCS.

Science.gov (United States)

Andoh, Tooru; Fujimoto, Takuya; Suzuki, Minoru; Sudo, Tamotsu; Sakurai, Yoshinori; Tanaka, Hiroki; Fujita, Ikuo; Fukase, Naomasa; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Toshiko; Sasai, Hiroshi; Kawamoto, Teruya; Kirihata, Mitsunori; Fukumori, Yoshinobu; Akisue, Toshihiro; Ono, Koji; Ichikawa, Hideki

2015-12-01

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases. Copyright © 2015 Elsevier Ltd. All rights reserved.

HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy.

Science.gov (United States)

Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

2016-08-18

This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.

Investigation of dose distribution in mixed neutron-gamma field of boron neutron capture therapy using N isopropylacrylamide gel

Energy Technology Data Exchange (ETDEWEB)

Bavarmegin, Elham; Sadremomtaz, Alireza [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Khalafi, Hossein; Kasesaz, Yaser [Dept. of Physics, University of Guilan, Rasht (Iran, Islamic Republic of); Khajeali, Azim [Medical Education Research Center, Tabriz (Iran, Islamic Republic of)

2017-02-15

Gel dosimeters have unique advantages in comparison with other dosimeters. Until now, these gels have been used in different radiotherapy techniques as a reliable dosimetric tool. Because dose distribution measurement is an important factor for appropriate treatment planning in different radiotherapy techniques, in this study, we evaluated the ability of the N-isopropylacrylamide (NIPAM) polymer gel to record the dose distribution resulting from the mixed neutron-gamma field of boron neutron capture therapy (BNCT). In this regard, a head phantom containing NIPAM gel was irradiated using the Tehran Research Reactor BNCT beam line, and then by a magnetic resonance scanner. Eventually, the R2 maps were obtained in different slices of the phantom by analyzing T2-weighted images. The results show that NIPAM gel has a suitable potential for recording three-dimensional dose distribution in mixed neutron-gamma field dosimetry.

Optimization of therapy of type 2 diabetes mellitus with the oral hypoglycemic agent glimepiride

Directory of Open Access Journals (Sweden)

Tatiana Ivanovna Romantsova

2010-03-01

Full Text Available Type 2 diabetes is believed to develop as a result of lowered insulin secretion and insulin resistance leading to hyperglycemia. Sulfonylureas stimulateinsulin secretion and thereby decrease blood glucose level which accounts for their wide application in the treatment of diabetes. However, manyagents of this class produce side effects (increased body mass, hypoglycemia, resistance to therapy, etc. attributable to excess stimulation of insulinsecretion. Glimepiride is as efficient as traditionally used sulfonylureas but causes a smaller rise in insulin secretion. Sulfonylurea receptors showlower affinity for glimepiride than for glibenclamide. Formation and dissociation of glimepiride-receptor complexes occur faster than those of glibenclamide-receptor complexes. In addition, therapeutic effect of glimepiride was shown to be associated with improved insulin sensitivity. It is concludedthat glimepiride is an efficacious agent for the treatment of type 2 diabetes.

Comparison of doses delivered in clinical trials of neutron capture therapy in the USA

International Nuclear Information System (INIS)

Albritton, J.R.; Binns, P.J.; Riley, K.J.; Coderre, J.A.; Harling, O.K.; Kiger, W.S. III

2006-01-01

A combined 81 brain tumor patients have been treated in dose escalation trials of Neutron Capture Therapy (NCT) at Harvard-MIT and Brookhaven National Laboratory (BNL). Pooling the clinical outcomes from these trials will permit evaluation with more statistical rigor. However, differences in physical and computational dosimetry between the institutions make direct comparison of the clinical dosimetry difficult. This paper describes work performed to normalize the BNL clinical dosimetry to that of Harvard-MIT for combined dose response analysis. This normalization involved analysis of MIT measurements and calculations using the BNL treatment planning system (TPS), BNCT - Rtpe, for two different phantoms. The BNL TPS was calibrated to dose measurements made by MIT at the BMRR in the BNL calibration phantom, a Lucite cube, and then validated by MIT dose measurements at the BMMR in an ellipsoidal water phantom. Treatment plans for all BNL patients were recomputed using the newly determined TPS calibration, yielding reductions in reported mean brain doses of 19% on average in the initial 15 patients and 31% in the latter 38 patients. These reductions in reported doses have clinically significant implications for those relying on reported BNL doses as a basis for initial dose selection in clinical studies. (author)

Sensing and capture of toxic and hazardous gases and vapors by metal-organic frameworks.

Science.gov (United States)

Wang, Hao; Lustig, William P; Li, Jing

2018-03-13

Toxic and hazardous chemical species are ubiquitous, predominantly emitted by anthropogenic activities, and pose serious risks to human health and the environment. Thus, the sensing and subsequent capture of these chemicals, especially in the gas or vapor phase, are of extreme importance. To this end, metal-organic frameworks have attracted significant interest, as their high porosity and wide tunability make them ideal for both applications. These tailorable framework materials are particularly promising for the specific sensing and capture of targeted chemicals, as they can be designed to fit a diverse range of required conditions. This review will discuss the advantages of metal-organic frameworks in the sensing and capture of harmful gases and vapors, as well as principles and strategies guiding the design of these materials. Recent progress in the luminescent detection of aromatic and aliphatic volatile organic compounds, toxic gases, and chemical warfare agents will be summarized, and the adsorptive removal of fluorocarbons/chlorofluorocarbons, volatile radioactive species, toxic industrial gases and chemical warfare agents will be discussed.

Targeting apoptotic machinery as approach for anticancer therapy: Smac mimetics as anticancer agents

Directory of Open Access Journals (Sweden)

Nevine M.Y. Elsayed

2015-06-01

Full Text Available Apoptosis is a chief regulator of cellular homeostasis. Impairment of apoptotic machinery is a main characteristic of several diseases such as cancer, where the evasion of apoptosis is a cardinal hallmark of cancer. Apoptosis is regulated by contribution of pro- and anti- apoptotic proteins, where caspases are the main executioners of the apoptotic machinery. IAP (inhibitors of apoptosis proteins is a family of endogenous inhibitors of apoptosis, which perform their function through interference with the function of caspases. Smac (second mitochondria-derived activator of caspases is endogenous inhibitor of IAPs, thus it is one of the major proapoptotic endogenous proteins. Thus, the development of Smac mimetics has evolved as an approach for anticancer therapy. Several Smac mimetic agents have been introduced to clinical trial such as birinapanet 12. Herein, the history of development of Smac mimetics along with the recent development in this field is briefly discussed.

Metal-organic frameworks for the removal of toxic industrial chemicals and chemical warfare agents.

Science.gov (United States)

Bobbitt, N Scott; Mendonca, Matthew L; Howarth, Ashlee J; Islamoglu, Timur; Hupp, Joseph T; Farha, Omar K; Snurr, Randall Q

2017-06-06

Owing to the vast diversity of linkers, nodes, and topologies, metal-organic frameworks can be tailored for specific tasks, such as chemical separations or catalysis. Accordingly, these materials have attracted significant interest for capture and/or detoxification of toxic industrial chemicals and chemical warfare agents. In this paper, we review recent experimental and computational work pertaining to the capture of several industrially-relevant toxic chemicals, including NH 3 , SO 2 , NO 2 , H 2 S, and some volatile organic compounds, with particular emphasis on the challenging issue of designing materials that selectively adsorb these chemicals in the presence of water. We also examine recent research on the capture and catalytic degradation of chemical warfare agents such as sarin and sulfur mustard using metal-organic frameworks.

Nutraceuticals as therapeutic agents for atherosclerosis.

Science.gov (United States)

Moss, Joe W E; Williams, Jessica O; Ramji, Dipak P

2018-05-01

Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all global deaths. Current treatments for CVD, such as optimized statin therapy, are associated with considerable residual risk and several side effects in some patients. The outcome of research on the identification of alternative pharmaceutical agents for the treatment of CVD has been relatively disappointing with many promising leads failing at the clinical level. Nutraceuticals, products from food sources with health benefits beyond their nutritional value, represent promising agents in the prevention of CVD or as an add-on therapy with current treatments. This review will highlight the potential of several nutraceuticals, including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti-CVD therapies based on clinical and pre-clinical mechanism-based studies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Potential of para-boronophenylalaninol as a boron carrier in boron neutron capture therapy, referring to that of its enantiomers

International Nuclear Information System (INIS)

Masunaga, S.; Sakurai, Y.; Ono, K.; Suziki, M.; Nagata, K.; Takagaki, M.; Nagasawa, H.

2003-01-01

We evaluated the potential of a newly developed 10 B-containing alpha-amino alcohol of para-boronophenylalanine- 10 B (BPA), para-boronophenylalaninol (BPAol), as a boron carrier in boron neutron capture therapy. C57BL mice bearing EL4 tumors and C3H/He mice bearing SCC VII 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. For the combination with mild temperature hyperthermia (MTH) and/or tirapazamine (TPZ), the tumors were heated at 40 degrees centigrade for 30 minutes right before neutron exposure, and/or TPZ was intraperitoneally injected 30 minutes 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 hours 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. Without TPZ or MTH, L- and D-BPAol increased both frequencies markedly, especially for total cells. Although not significantly, L-BPA and D-BPAol increased both frequencies slightly more remarkably than D-BPA and L-BPAol, respectively. On combined treatment with both MTH and TPZ, the sensitivity difference between total and Q cells was markedly reduced. MTH increased the 10 B uptake of all 10 B-carriers into both tumor cells to some degree. Both L- and D-BPAol have potential as 10 B-carriers in neutron capture therapy, especially when combined with both MTH and TPZ

Magnetizable stent-grafts enable endothelial cell capture

Energy Technology Data Exchange (ETDEWEB)

Tefft, Brandon J. [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Uthamaraj, Susheil [Division of Engineering, Mayo Clinic, Rochester, MN (United States); Harburn, J. Jonathan [School of Medicine, Pharmacy and Health, Durham University, Stockton-on-Tees (United Kingdom); Hlinomaz, Ota [Department of Cardioangiology, St. Anne' s University Hospital, Brno (Czech Republic); Lerman, Amir [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States); Dragomir-Daescu, Dan [Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN (United States); Sandhu, Gurpreet S., E-mail: sandhu.gurpreet@mayo.edu [Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (United States)

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance. - Highlights: • Magnetic stent-grafts were made from 2205 steel stents and polyurethane nanofibers. • Stent-grafts remained patent and formed a thin and uniform neointima when implanted. • Stent-grafts captured endothelial cells labeled with magnetic nanoparticles. �

Accelerator-Based Boron Neutron Capture Therapy and the Development of a Dedicated Tandem-Electrostatic-Quadrupole

International Nuclear Information System (INIS)

Kreiner, A. J.; Di Paolo, H.; Burlon, A. A.; Valda, A. A.; Debray, M. E.; Somacal, H. R.; Minsky, D. M.; Kesque, J. M.; Giboudot, Y.; Levinas, P.; Fraiman, M.; Romeo, V.

2007-01-01

There is a generalized perception that the availability of suitable particle accelerators installed in hospitals, as neutron sources, may be crucial for the advancement of Boron Neutron Capture Therapy (BNCT). Progress on an ongoing project to develop a Tandem-ElectroStatic-Quadrupole (TESQ) accelerator for Accelerator-Based (AB)-BNCT is described here. The project goal is a machine capable of delivering 30 mA of 2.5 MeV protons to be used in conjunction with a neutron production target based on the 7 Li(p,n) 7 Be reaction slightly beyond its resonance at 2.25 MeV. A folded tandem, with 1.25 MV terminal voltage, combined with an ESQ chain is being designed and constructed. A 30 mA proton beam of 2.5 MeV are the specifications needed to produce sufficiently intense and clean epithermal neutron beams, based on the 7 Li(p,n) 7 Be reaction, to perform BNCT treatment for deep-seated tumors in less than an hour. The first design and construction of an ESQ module is discussed and its electrostatic fields are investigated theoretically and experimentally. Also new beam transport calculations through the accelerator are presented

LED and low level laser therapy association in tooth bleaching using a novel low concentration H2O2/N-doped TiO2 bleaching agent

Science.gov (United States)

Bezerra Dias, Hércules; Teixeira Carrera, Emanuelle; Freitas Bortolatto, Janaína; Ferrarezi de Andrade, Marcelo; Nara de Souza Rastelli, Alessandra

2016-01-01

Since low concentration bleaching agents containing N-doped TiO2 nanoparticles have been introduced as an alternative to conventional agents, it is important to verify their efficacy and the hypersensitivity effect in clinical practice. Six volunteer patients were evaluated for color change and hypersensitivity after bleaching using 35% H2O2 (one session of two 12 min applications) and 6% H2O2/N-doped TiO2 (one session of three 12 min applications) and after low level laser therapy application (LLLT) (780 nm, 40 mW, 10 J.cm-2, 10 s). Based on this case study, the nanobleaching agent provided better or similar aesthetic results than the conventional agent under high concentration, and its association with LLLT satisfactorily decreased the hypersensitivity. The 6% H2O2/N-doped TiO2 agent could be used instead of conventional in-office bleaching agents under high concentrations to fulfill the rising patient demand for aesthetics.

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

Energy Technology Data Exchange (ETDEWEB)

Bakeine, G.J. [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste (Italy)], E-mail: jamesbakeine1@yahoo.com; Di Salvo, M. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bortolussi, S.; Stella, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); Bertolotti, A.; Nano, R. [Department of Animal Biology University of Pavia, Piazza Botta, Pavia (Italy); Clerici, A.; Ferrari, C.; Zonta, C. [Department of Surgery University of Pavia, Piazza Botta, Pavia (Italy); Marchetti, A. [Scientific Research Office, Fondazione San Matteo University Policlinic, Pavia (Italy); Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Via Bassi 6, Pavia (Italy); National Institute of Nuclear Physics (INFN) Section of Pavia, Via Bassi 6, Pavia (Italy)

2009-07-15

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Feasibility study on the utilization of boron neutron capture therapy (BNCT) in a rat model of diffuse lung metastases

International Nuclear Information System (INIS)

Bakeine, G.J.; Di Salvo, M.; Bortolussi, S.; Stella, S.; Bruschi, P.; Bertolotti, A.; Nano, R.; Clerici, A.; Ferrari, C.; Zonta, C.; Marchetti, A.; Altieri, S.

2009-01-01

In order for boron neutron capture therapy (BNCT) to be eligible for application in lung tumour disease, three fundamental criteria must be fulfilled: there must be selective uptake of boron in the tumour cells with respect to surrounding healthy tissue, biological effectiveness of the radiation therapy and minimal damage or collateral effects of the irradiation on the surrounding tissues. In this study, we evaluated the biological effectiveness of BNCT by in vitro irradiation of rat colon-carcinoma cells previously incubated in boron-enriched medium. One part of these cells was re-cultured in vitro while the other was inoculated via the inferior vena cava to induce pulmonary metastases in a rat model. We observed a post-irradiation in vitro cell viability of 0.05% after 8 days of cell culture. At 4 months follow-up, all animal subjects in the treatment group that received irradiated boron-containing cells were alive. No animal survived beyond 1 month in the control group that received non-treated cells (p<0.001 Kaplan-Meier). These preliminary findings strongly suggest that BNCT has a significant lethal effect on tumour cells and post irradiation surviving cells lose their malignant capabilities in vivo. This radio-therapeutic potential warrants the investigation of in vivo BNCT for lung tumour metastases.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer

International Nuclear Information System (INIS)

Suzuki, Minoru; Kato, Ituro; Aihara, Teruhito

2014-01-01

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10–12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7–40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted. (author)

Inorganic membranes for carbon capture and power generation

Science.gov (United States)

Snider, Matthew T.

Inorganic membranes are under consideration for cost-effective reductions of carbon emissions from coal-fired power plants, both in the capture of pollutants post-firing and in the direct electrochemical conversion of coal-derived fuels for improved plant efficiency. The suitability of inorganic membrane materials for these purposes stems as much from thermal and chemical stability in coal plant operating conditions as from high performance in gas separations and power generation. Hydrophilic, micro-porous zeolite membrane structures are attractive for separating CO2 from N2 in gaseous waste streams due to the attraction of CO2 to the membrane surface and micropore walls that gives the advantage to CO2 transport. Recent studies have indicated that retention of the templating agent used in zeolite synthesis can further block N2 from the micropore interior and significantly improve CO2/N2 selectivity. However, the role of the templating agent in micro-porous transport has not been well investigated. In this work, gas sorption studies were conducted by high-pressure thermo-gravimetric analysis on Zeolite Y membrane materials to quantify the effect of the templating agent on CO2, N2, and H2O adsorption/desorption, as well as to examine the effect of humidification on overall membrane performance. In equilibrium conditions, the N2 sorption enthalpy was nearly unchanged by the presence of the templating agent, but the N2 pore occupation was reduced ˜1000x. Thus, the steric nature of the blocking of N2 from the micropores by the templating agent was confirmed. CO2 and H2O sorption enthalpies were similarly unaffected by the templating agent, and the micropore occupations were only reduced as much as the void volume taken up by the templating agent. Thus, the steric blocking effect did not occur for molecules more strongly attracted to the micropore walls. Additionally, in time-transient measurements the CO 2 and H2O mobilities were significantly enhanced by the presence

Mn2+-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy.

Science.gov (United States)

Xi, Juqun; Da, Lanyue; Yang, Changshui; Chen, Rui; Gao, Lizeng; Fan, Lei; Han, Jie

2017-01-01

Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn 2+ -coordinated doxorubicin (DOX)-loaded poly(lactic- co -glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn 2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn 2+ -PDA@DOX/PLGA nanoparticles. In our system, Mn 2+ -PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn 2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn 2+ -PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties.

Radioprotective agents to reduce BNCT (Boron Neutron Capture Therapy) induced mucositis in the hamster cheek pouch; Agentes radioprotectores para reducir la mucositis inducida por la terapia por captura neutrónica en boro (BNCT) en la bolsa de la mejilla del hámster

Energy Technology Data Exchange (ETDEWEB)

Monti Hughes, A. [Dpto. de Radiobiología, Gerencia de Química Nuclear y Ciencias de la Salud, GAATEN, Comisión Nacional de Energía Atómica (CNEA) (Argentina); Pozzi, E. C.C. [Gerencia de Reactores de Investigación y Producción, GAATEN, CNEA (Argentina); Thorp, S., E-mail: andrea.monti@cnea.gov.ar [Sub-Gerencia Instrumentación y Control, GAEN, CNEA(Argentina)

2013-07-01

Introduction: BNCT is based on the capture reaction between boron, selectively targeted to tumor tissue, and thermal neutrons which gives rise to lethal, short-range high linear energy transfer particles that selectively damage tumor tissue, sparing normal tissue. We previously evidenced a remarkable therapeutic success of BNCT mediated by boronophenylalanine (BPA) in the hamster cheek pouch oral cancer and pre cancer model. Despite therapeutic efficacy, mucositis induced in premalignant tissue was dose limiting and favored, in some cases, tumor development. In a clinical scenario, oral mucositis limits the dose administered to head and neck tumors. Aim: Our aim was to evaluate the effect of the administration of different radioprotective agents, seeking to reduce BNCT-induced mucositis to acceptable levels in dose-limiting premalignant tissue; without compromising therapeutic effect evaluated as inhibition on tumor development in premalignant tissue; without systemic or local side effects; and without negative effects on the biodistribution of the boron compound used for treatment. Materials and methods: Cancerized hamsters with DMBA (dimethylbenzanthracene) were treated with BPA-BNCT 5 Gy total absorbed dose to premalignant tissue, at the RA-3 Nuclear Reactor, divided into different groups: 1-treated with FLUNIXIN; 2- ATORVASTATIN; 3-THALIDOMIDE; 4-HISTAMINE (two concentrations: Low -1 mg/ml- and High -5 mg/ml-); 5-JNJ7777120; 6-JNJ10191584; 7-SALINE (vehicle). Cancerized animals without any treatment (neither BNCT nor radioprotective therapy) were also analyzed. We followed the animals during one month and evaluated the percentage of animals with unacceptable/severe mucositis, clinical status and percentage of animals with new tumors post treatment. We also performed a preliminary biodistribution study of BPA + Histamine “low” concentration to evaluate the potential effect of the radioprotector on BPA biodistribution. Results: Histamine �

THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

Directory of Open Access Journals (Sweden)

Xenofon Papanikolaou

2011-10-01

Full Text Available Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

THERAPY-RELATED MYELOID MALIGNANCIES IN MYELOMA

Directory of Open Access Journals (Sweden)

Bart Barlogie

2011-01-01

Full Text Available

Therapy related myeloid malignancies are an increasingly recognized treatment complication in patients undergoing therapy for multiple myeloma. The main predisposing factors are the alkylating agents, topoisomerase II inhibitors and radiotherapy, but recently questions have been raised regarding the immunomodulatory agent lenalidomide. Little is known about the new antimyeloma agents in the context of therapy related myeloid malignanices. The duration of treatment and the time from diagnosis are the main contributing factors in alkylating induced myeloid malignancies which occur 5-10 years after treatment, chromosome 5 and 7 abnormalities being the characteristic finding. High dose therapy (HDT does not seem to be a major contributing factor per se in multiple myeloma. In a number of large published series, all the factors related with therapy-induced myelodysplasia were defined prior to HDT. Topoisomerase II inhibitors induce mainly acute leukemias which invariably correlate with dysregulation of the MLL gene. Radiotherapy causes therapy related myelodysplasia if applied in bone marrow producing areas, especially if combined with chemotherapy. Therapy related myeloid malignancies generally herald a poor prognosis. Karyotypic abnormalities seem to be the main prognostic factor. In all cases the risk for therapy related myeloid malignancies drops sharply by 10 years after the treatment.

Perspective on future therapy of vasculitis.

Science.gov (United States)

Boumpas, D T; Kritikos, H D; Daskalakis, N G

2000-10-01

This article summarizes recent advances in the management of various vasculitic syndromes and discusses potential new therapies based on a better understanding of their pathogenesis and natural history. Current efforts for optimization of testing for antineutrophil cytoplasmic antibodies and improvement of diagnostic criteria will certainly have a significant impact on future therapy. Biologic agents such as interferon-alpha are already in use in various vasculitides, whereas others, such as inhibitors of tumor necrosis factor-alpha, are in phase I clinical trials. Agents that selectively inhibit distinct steps in the pathogenesis of vasculitis are in preclinical or early clinical stages of development. Newer (mycophenolate mofetil, leflunamide) or older (methotrexate, azathioprine) immunosuppresive agents are finding new roles in the management of vasculitides. For patients with severe vasculitis, short-term use of cytotoxic agents, such as cyclophosphamide, alone or in combination with biologic agents, may expedite remission, which could then be better maintained with other, less toxic (and less expensive) immunosuppressive agents, such as methotrexate, azathioprine, mycophenolate mofetil, and leflunamide. For patients with mild or moderately severe vasculitis, these latter agents alone may be adequate. New therapeutic studies in vasculitis should better address the impact of therapy on health-related quality of life and its long-term toxicity.

Magnetizable stent-grafts enable endothelial cell capture

Science.gov (United States)

Tefft, Brandon J.; Uthamaraj, Susheil; Harburn, J. Jonathan; Hlinomaz, Ota; Lerman, Amir; Dragomir-Daescu, Dan; Sandhu, Gurpreet S.

2017-04-01

Emerging nanotechnologies have enabled the use of magnetic forces to guide the movement of magnetically-labeled cells, drugs, and other therapeutic agents. Endothelial cells labeled with superparamagnetic iron oxide nanoparticles (SPION) have previously been captured on the surface of magnetizable 2205 duplex stainless steel stents in a porcine coronary implantation model. Recently, we have coated these stents with electrospun polyurethane nanofibers to fabricate prototype stent-grafts. Facilitated endothelialization may help improve the healing of arteries treated with stent-grafts, reduce the risk of thrombosis and restenosis, and enable small-caliber applications. When placed in a SPION-labeled endothelial cell suspension in the presence of an external magnetic field, magnetized stent-grafts successfully captured cells to the surface regions adjacent to the stent struts. Implantation within the coronary circulation of pigs (n=13) followed immediately by SPION-labeled autologous endothelial cell delivery resulted in widely patent devices with a thin, uniform neointima and no signs of thrombosis or inflammation at 7 days. Furthermore, the magnetized stent-grafts successfully captured and retained SPION-labeled endothelial cells to select regions adjacent to stent struts and between stent struts, whereas the non-magnetized control stent-grafts did not. Early results with these prototype devices are encouraging and further refinements will be necessary in order to achieve more uniform cell capture and complete endothelialization. Once optimized, this approach may lead to more rapid and complete healing of vascular stent-grafts with a concomitant improvement in long-term device performance.

Building an Educational Program together health community agents

Directory of Open Access Journals (Sweden)

Lúcia Rondelo Duarte

2007-01-01

Full Text Available Aiming at contributing inputs to the learning process of community health agents from Family Health Strategy, this study has sought to devise an Educational Program to qualify seven community agents from the Family Health Unit on Habiteto, a neighborhood in the Brazilian city of Sorocaba. Speeches on the perception these agents have of their work, their difficulties and proposals were captured and analyzed within the framework of the "Collective Subject Speech". Results showed the group's learning needs, and guided the devising and implementation of the Educational Program, which adopted the "Problem-Based Education" model. This knowledge was built by the agents through a problem-focused reality, debating, searching for solutions, and implementing intervention projects. They noticed that being a community health agent means, above all, to struggle and harness community forces for purposes of defending health & education public services and for improving social health determinants.

Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

Science.gov (United States)

D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

2017-01-01

Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

Learning in engineered multi-agent systems

Science.gov (United States)

Menon, Anup

Consider the problem of maximizing the total power produced by a wind farm. Due to aerodynamic interactions between wind turbines, each turbine maximizing its individual power---as is the case in present-day wind farms---does not lead to optimal farm-level power capture. Further, there are no good models to capture the said aerodynamic interactions, rendering model based optimization techniques ineffective. Thus, model-free distributed algorithms are needed that help turbines adapt their power production on-line so as to maximize farm-level power capture. Motivated by such problems, the main focus of this dissertation is a distributed model-free optimization problem in the context of multi-agent systems. The set-up comprises of a fixed number of agents, each of which can pick an action and observe the value of its individual utility function. An individual's utility function may depend on the collective action taken by all agents. The exact functional form (or model) of the agent utility functions, however, are unknown; an agent can only measure the numeric value of its utility. The objective of the multi-agent system is to optimize the welfare function (i.e. sum of the individual utility functions). Such a collaborative task requires communications between agents and we allow for the possibility of such inter-agent communications. We also pay attention to the role played by the pattern of such information exchange on certain aspects of performance. We develop two algorithms to solve this problem. The first one, engineered Interactive Trial and Error Learning (eITEL) algorithm, is based on a line of work in the Learning in Games literature and applies when agent actions are drawn from finite sets. While in a model-free setting, we introduce a novel qualitative graph-theoretic framework to encode known directed interactions of the form "which agents' action affect which others' payoff" (interaction graph). We encode explicit inter-agent communications in a directed

Synovectomy by Neutron capture

International Nuclear Information System (INIS)

Vega C, H.R.; Torres M, C.

1998-01-01

The Synovectomy by Neutron capture has as purpose the treatment of the rheumatoid arthritis, illness which at present does not have a definitive curing. This therapy requires a neutron source for irradiating the articulation affected. The energy spectra and the intensity of these neutrons are fundamental since these neutrons induce nuclear reactions of capture with Boron-10 inside the articulation and the freely energy of these reactions is transferred at the productive tissue of synovial liquid, annihilating it. In this work it is presented the neutron spectra results obtained with moderator packings of spherical geometry which contains in its center a Pu 239 Be source. The calculations were realized through Monte Carlo method. The moderators assayed were light water, heavy water base and the both combination of them. The spectra obtained, the average energy, the neutron total number by neutron emitted by source, the thermal neutron percentage and the dose equivalent allow us to suggest that the moderator packing more adequate is what has a light water thickness 0.5 cm (radius 2 cm) and 24.5 cm heavy water (radius 26.5 cm). (Author)

Application of drug delivery system to boron neutron capture therapy for cancer.

Science.gov (United States)

Yanagië, Hironobu; Ogata, Aya; Sugiyama, Hirotaka; Eriguchi, Masazumi; Takamoto, Shinichi; Takahashi, Hiroyuki

2008-04-01

Tumor cell destruction in boron neutron capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons ((10)B + (1)n --> (7)Li + (4)He (alpha) + 2.31 MeV (93.7 %)/2.79 MeV (6.3 %)). The resulting lithium ions and alphaparticles are high linear energy transfer (LET) particles which give a high biological effect. Their short range in tissue (5 - 9 mum) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma. Sodium mercaptoundecahydro-dodecaborate (Na(2)(10)B(12)H(11)SH: BSH) and borono-phenylalanine ((10)BPA) are currently being used in clinical treatments. These low molecule compounds are easily cleared from cancer cells and blood, so high accumulation and selective delivery of boron compounds into tumor tissues and cancer cells are most important to achieve effective BNCT and to avoid damage to adjacent healthy cells. In order to achieve the selective delivery of boron atoms to cancer cells, a drug delivery system (DDS) is an attractive intelligent technology for targeting and controlled release of drugs. We performed literature searches related to boron delivery systems in vitro and in vivo. We describe several DDS technologies for boron delivery to cancer tissues and cancer cells from the past to current status. We are convinced that it will be possible to use liposomes, monoclonal antibodies and WOW emulsions as boron delivery systems for BNCT clinically in accordance with the preparation of good commercial product (GCP) grade materials.

Liposome imaging agents in personalized medicine

DEFF Research Database (Denmark)

Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto

2012-01-01

In recent years the importance of molecular and diagnostic imaging has increased dramatically in the treatment planning of many diseases and in particular in cancer therapy. Within nanomedicine there are particularly interesting possibilities for combining imaging and therapy. Engineered liposomes...... that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...

Can We Predict the Efficacy of Anti-TNF-α Agents?

Science.gov (United States)

Lopetuso, Loris Riccardo; Gerardi, Viviana; Papa, Valerio; Scaldaferri, Franco; Rapaccini, Gian Lodovico; Gasbarrini, Antonio; Papa, Alfredo

2017-09-14

The use of biologic agents, particularly anti-tumor necrosis factor (TNF)-α, has revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Several data on the efficacy of these agents in inducing and maintaining clinical remission have been accumulated over the past two decades: their use avoid the need for steroids therapy, promote mucosal healing, reduce hospitalizations and surgeries and therefore dramatically improve the quality of life of IBD patients. However, primary non-response to these agents or loss of response over time mainly due to immunogenicity or treatment-related side-effects are a frequent concern in IBD patients. Thus, the identification of predicting factors of efficacy is crucial to allow clinicians to efficiently use these therapies, avoiding them when they are ineffective and eventually shifting towards alternative biological therapies with the end goal of optimizing the cost-effectiveness ratio. In this review, we aim to identify the predictive factors of short- and long-term benefits of anti-TNF-α therapy in IBD patients. In particular, multiple patient-, disease- and treatment-related factors have been evaluated.

Design of neutron beams at the Argonne Continuous Wave Linac (ACWL) for boron neutron capture therapy and neutron radiography

International Nuclear Information System (INIS)

Zhou, X.L.; McMichael, G.E.

1994-01-01

Neutron beams are designed for capture therapy based on p-Li and p-Sc reactions using the Argonne Continuous Wave Linac (ACWL). The p-Li beam will provide a 2.5 x 10 9 n/cm 2 s epithermal flux with 7 x 10 5 γ/cm 2 s contamination. On a human brain phantom, this beam allows an advantage depth (AD) of 10 cm, an advantage depth dose rate (ADDR) of 78 cGy/min and an advantage ratio (AR) of 3.2. The p-Sc beam offers 5.9 x 10 7 n/cm 2 s and a dose performance of AD = 8 cm and AR = 3.5, suggesting the potential of near-threshold (p,n) reactions such as the p-Li reaction at E p = 1.92 MeV. A thermal radiography beam could also be obtained from ACWL

Interactive Embodied Agents for Cultural Heritage and Archaeological presentations

Directory of Open Access Journals (Sweden)

F. Seron

2010-04-01

Full Text Available In this paper, Maxine, a powerful engine to develop applications with embodied animated agents is presented. The engine, based on the use of open source libraries, enables multimodal real-time interaction with the user: via text, voice, images and gestures. Maxine virtual agents can establish emotional communication with the user through their facial expressions, the modulation of the voice and expressing the answers of the agents according to the information gathered by the system: noise level in the room, observer’s position, emotional state of the observer, etc. Moreover, the user’s emotions are considered and captured through images. For the moment, Maxine virtual agents have been used as virtual presenters for Cultural Heritage and Archaeological shows.

Beyond Alkylating Agents for Gliomas: Quo Vadimus?

Science.gov (United States)

Puduvalli, Vinay K; Chaudhary, Rekha; McClugage, Samuel G; Markert, James

2017-01-01

Recent advances in therapies have yielded notable success in terms of improved survival in several cancers. However, such treatments have failed to improve outcome in patients with gliomas for whom surgery followed by radiation therapy and chemotherapy with alkylating agents remain the standard of care. Genetic and epigenetic studies have helped identify several alterations specific to gliomas. Attempts to target these altered pathways have been unsuccessful due to various factors, including tumor heterogeneity, adaptive resistance of tumor cells, and limitations of access across the blood-brain barrier. Novel therapies that circumvent such limitations have been the focus of intense study and include approaches such as immunotherapy, targeting of signaling hubs and metabolic pathways, and use of biologic agents. Immunotherapeutic approaches including tumor-targeted vaccines, immune checkpoint blockade, antibody-drug conjugates, and chimeric antigen receptor-expressing cell therapies are in various stages of clinical trials. Similarly, identification of key metabolic pathways or converging hubs of signaling pathways that are tumor specific have yielded novel targets for therapy of gliomas. In addition, the failure of conventional therapies against gliomas has led to a growing interest among patients in the use of alternative therapies, which in turn has necessitated developing evidence-based approaches to the application of such therapies in clinical studies. The development of these novel approaches bears potential for providing breakthroughs in treatment of more meaningful and improved outcomes for patients with gliomas.

Ultrasound-induced Gas Release from Contrast Agent Microbubbles

NARCIS (Netherlands)

Postema, M.A.B.; Postema, Michiel; Bouakaz, Ayache; Versluis, Michel; de Jong, N.

2005-01-01

We investigated gas release from two hard-shelled ultrasound contrast agents by subjecting them to high-mechanical index (MI) ultrasound and simultaneously capturing high-speed photographs. At an insonifying frequency of 1.7 MHz, a larger percentage of contrast bubbles is seen to crack than at 0.5

The need for and development of behaviourally realistic agents

NARCIS (Netherlands)

Jager, W; Janssen, M; Sichman, JS; Bousquet, F; Davidsson, P

2003-01-01

In this paper we argue that simulating complex systems involving human behaviour requires agent rules based on a theoretically rooted structure that captures basic behavioural processes. Essential components of such a structure involve needs, decision-making processes and learning. Such a structure

Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

Science.gov (United States)

Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

2012-01-01

Objectives 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. Methods 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. Results 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. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

Article Commentary: Chelation Therapy for Mercury Poisoning

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Rong Guan

2009-01-01

Full Text Available Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role of chelating agents against mercury poisoning, which provides a promising research direction for broader application of chelation therapy in prevention and treatment of mercury poisoning.

Boron neutron capture therapy using mixed epithermal and thermal neutron beams in patients with malignant glioma-correlation between radiation dose and radiation injury and clinical outcome

International Nuclear Information System (INIS)

Kageji, Teruyoshi; Nagahiro, Shinji; Matsuzaki, Kazuhito; Mizobuchi, Yoshifumi; Toi, Hiroyuki; Nakagawa, Yoshinobu; Kumada, Hiroaki

2006-01-01

Purpose: To clarify the correlation between the radiation dose and clinical outcome of sodium borocaptate-based intraoperative boron neutron capture therapy in patients with malignant glioma. Methods and Materials: The first protocol (P1998, n = 8) prescribed a maximal gross tumor volume (GTV) dose of 15 Gy. In 2001, a dose-escalated protocol was introduced (P2001, n 11), which prescribed a maximal vascular volume dose of 15 Gy or, alternatively, a clinical target volume (CTV) dose of 18 Gy. Results: The GTV and CTV doses in P2001 were 1.1-1.3 times greater than those in P1998. The maximal vascular volume dose of those with acute radiation injury was 15.8 Gy. The mean GTV and CTV dose in long-term survivors with glioblastoma was 26.4 and 16.5 Gy, respectively. A statistically significant correlation between the GTV dose and median survival time was found. In the 11 glioblastoma patients in P2001, the median survival time was 19.5 months and 1- and 2-year survival rate was 60.6% and 37.9%, respectively. Conclusion: Dose escalation contributed to the improvement in clinical outcome. To avoid radiation injury, the maximal vascular volume dose should be <12 Gy. For long-term survival in patients with glioblastoma after boron neutron capture therapy, the optimal mean dose of the GTV and CTV was 26 and 16 Gy, respectively

Pharmacological therapy for amblyopia

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Anupam Singh

2017-01-01

Full Text Available Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time, penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

Pharmacological therapy for amblyopia

Science.gov (United States)

Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

2017-01-01

Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

Elite Capture and Corruption in two Villages in Bengkulu Province, Sumatra.

Science.gov (United States)

Lucas, Anton

This paper examines leadership, elite capture and corruption in two villages in Sumatra. It compares implementation and outcomes of several conservation and development projects in the context of democratization and decentralization reforms introduced in Indonesia since 1998. In examining aspects of elite control and elite capture, this paper focuses on the activities of local elites, particularly village officials, who use their positions to monopolize planning and management of projects that were explicitly intended to incorporate participatory and accountability features. While elites' use of authority and influence to benefit personally from their roles clearly reflects elite capture, there are nonetheless members of elite groups in these case studies who use their control of projects to broad community benefit. In both villages there is considerable friction between villagers and elites as well as among members of the local elite themselves over control of local resources. Differences in the structure of these cross-cutting internal relationships and of ties between local authorities and outside government and non-government agents largely explain the differences in degree of elite capture and its outcomes in the two cases.

Development of Ocular Delivery System for Glaucoma Therapy Using Natural Hydrogel as Film Forming Agent and Release Modifier.

Science.gov (United States)

Kulkarni, Giriraj T; Sethi, Nitin; Awasthi, Rajendra; Pawar, Vivek Kumar; Pahuja, Vineet

2016-01-01

Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug. The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops. The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies. The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye. It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

Perspectives in the development of hybrid bifunctional antitumour agents.

Science.gov (United States)

Musso, Loana; Dallavalle, Sabrina; Zunino, Franco

2015-08-15

In spite of the development of a large number of novel target-specific antitumour agents, the single-agent therapy is in general not able to provide an effective durable control of the malignant process. The limited efficacy of the available agents (both conventional cytotoxic and novel target-specific) reflects not only the expression of defence mechanisms, but also the complexity of tumour cell alterations and the redundancy of survival pathways, thus resulting in tumour cell ability to survive under stress conditions. A well-established strategy to improve the efficacy of antitumour therapy is the rational design of drug combinations aimed at achieving synergistic effects and overcoming drug resistance. An alternative strategy could be the use of agents designed to inhibit simultaneously multiple cellular targets relevant to tumour growth/survival. Among these novel agents are hybrid bifunctional drugs, i.e. compounds resulting by conjugation of different drugs or containing the pharmocophores of different drugs. This strategy has been pursued using various conventional or target-specific agents (with DNA damaging agents and histone deacetylase inhibitors as the most exploited compounds). A critical overview of the most representative compounds is provided with emphasis on the HDAC inhibitor-based hybrid agents. In spite of some promising results, the actual pharmacological advantages of the hybrid agents remain to be defined. This commentary summarizes the recent advances in this field and highlights the pharmacological basis for a rational design of hybrid bifunctional agents. Copyright © 2015. Published by Elsevier Inc.

Modern antiplatelet agents in coronary artery disease.

LENUS (Irish Health Repository)

Power, Rachel F

2012-10-01

Dual antiplatelet therapy is well recognized in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Despite clinical benefits of aspirin and clopidogrel therapy, a number of limitations curtail their efficacy: slow onset of action, variability in platelet inhibitory response and potential drug-drug interactions. Furthermore, the single platelet-activation pathway targeted by these agents allows continued platelet activation via other pathways, ensuring incomplete protection against ischemic events, thus, underscoring the need for alternate antiplatelet treatment strategies. A number of novel antiplatelet agents are currently in advance development and many have established superior effects on platelet inhibition, clinical outcomes and safety profile than clopidogrel in high-risk patients. The aim of this review is to provide an overview of the current status of P2Y12 receptor inhibition and PAR-1 antagonists in determining a future strategy for individualized antiplatelet therapy.

TU-FG-BRB-07: GPU-Based Prompt Gamma Ray Imaging From Boron Neutron Capture Therapy

Energy Technology Data Exchange (ETDEWEB)

Kim, S; Suh, T; Yoon, D; Jung, J; Shin, H; Kim, M [The catholic university of Korea, Seoul (Korea, Republic of)

2016-06-15

Purpose: The purpose of this research is to perform the fast reconstruction of a prompt gamma ray image using a graphics processing unit (GPU) computation from boron neutron capture therapy (BNCT) simulations. Methods: To evaluate the accuracy of the reconstructed image, a phantom including four boron uptake regions (BURs) was used in the simulation. After the Monte Carlo simulation of the BNCT, the modified ordered subset expectation maximization reconstruction algorithm using the GPU computation was used to reconstruct the images with fewer projections. The computation times for image reconstruction were compared between the GPU and the central processing unit (CPU). Also, the accuracy of the reconstructed image was evaluated by a receiver operating characteristic (ROC) curve analysis. Results: The image reconstruction time using the GPU was 196 times faster than the conventional reconstruction time using the CPU. For the four BURs, the area under curve values from the ROC curve were 0.6726 (A-region), 0.6890 (B-region), 0.7384 (C-region), and 0.8009 (D-region). Conclusion: The tomographic image using the prompt gamma ray event from the BNCT simulation was acquired using the GPU computation in order to perform a fast reconstruction during treatment. The authors verified the feasibility of the prompt gamma ray reconstruction using the GPU computation for BNCT simulations.

An accelerator-based Boron Neutron Capture Therapy (BNCT) facility based on the 7Li(p,n)7Be

Science.gov (United States)

Musacchio González, Elizabeth; Martín Hernández, Guido

2017-09-01

BNCT (Boron Neutron Capture Therapy) is a therapeutic modality used to irradiate tumors cells previously loaded with the stable isotope 10B, with thermal or epithermal neutrons. This technique is capable of delivering a high dose to the tumor cells while the healthy surrounding tissue receive a much lower dose depending on the 10B biodistribution. In this study, therapeutic gain and tumor dose per target power, as parameters to evaluate the treatment quality, were calculated. The common neutron-producing reaction 7Li(p,n)7Be for accelerator-based BNCT, having a reaction threshold of 1880.4 keV, was considered as the primary source of neutrons. Energies near the reaction threshold for deep-seated brain tumors were employed. These calculations were performed with the Monte Carlo N-Particle (MCNP) code. A simple but effective beam shaping assembly (BSA) was calculated producing a high therapeutic gain compared to previously proposed facilities with the same nuclear reaction.

Antiplatelet therapy in PCI

Science.gov (United States)

Fanaroff, Alexander; Rao, Sunil

2018-01-01

Platelets play a key role in mediating stent thrombosis, the major cause of ischemic events in the immediate period following percutaneous coronary intervention (PCI). For this reason, antiplatelet therapy, started at the time of PCI and continued for at least 30 days afterwards, is the cornerstone of antithrombotic therapy after PCI. However, the use of antiplatelet agents increase bleeding risk, with more potent antiplatelet agents further increasing bleeding risk. For this reason, balancing prevention of ischemic events with risk of bleeding is fundamental to the effective use of antiplatelet agents. In the past 5 years, potent and fast-acting P2Y12 inhibitors have been introduced, and have augmented the antiplatelet armamentarium available to interventional cardiologists. In this review, we review the preclinical and clinical data surrounding these new agents, and discuss the significant questions and controversies that still exist regarding the optimal antiplatelet strategy. PMID:28582206

Advances in the use of biologic agents for the treatment of systemic vasculitis

Science.gov (United States)

Chung, Sharon A.; Seo, Philip

2010-01-01

Purpose of review Due to the well-known toxicities of cyclophosphamide, substantial interest exists in finding other therapies to treat primary systemic vasculitis. Biologic agents have been proposed as an alternative to cyclophosphamide for these disorders because of their recent success in treating other rheumatic diseases. This article reviews the current state-of-the-art with regards to the use of biologic agents as a treatment for systemic vasculitis. Recent findings The greatest amount of experience with these agents for the treatment of systemic vasculitis is with anti-tumor necrosis factor agents, pooled intravenous immunoglobulin, and anti-B cell therapies such as rituximab. Intravenous immunoglobulin is already a standard therapy for Kawasaki's disease, but should also be considered for the treatment of ANCA-associated vasculitis when standard therapies are either ineffective or contraindicated. Early experience with tumor necrosis factor inhibitors indicates that they may be effective for the treatment of Takayasu's arteritis, but their role in the treatment of other forms of vasculitis remains controversial. Early experience with rituximab for the treatment of several forms of vasculitis has been quite promising, but must be confirmed by ongoing randomized clinical trials. Summary Biologic agents represent the next evolution in treatment for the primary systemic vasculitides. Greater understanding of these diseases has allowed use to move further away from non-specific, highly toxic therapies towards a more directed approach. As our experience with these agents increases, they will likely form the keystone of treatment in the near future. PMID:19077713

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models

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Charles A Maitz

2017-08-01

Full Text Available Boron neutron capture therapy (BNCT was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH3(CH215–7,8-C2B9H11] in the lipid bilayer and encapsulated Na3[1-(2`-B10H9-2-NH3B10H8] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. Despite relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.

Monitoring of blood-10B concentration for boron neutron capture therapy using prompt gamma-ray analysis

International Nuclear Information System (INIS)

Raaijmakers, C.P.J.; Konijnenberg, M.W.; Dewit, L.; Mijnheer, B.J.; Haritz, D.; Huiskamp, R.; Philipp, K.; Siefert, A.; Stecher-Rasmussen, F.

1995-01-01

The aim of the present study was to monitor the blood- 10 B concentration of laboratory dogs receiving boron neutron capture therapy, in order to obtain optimal agreement between prescribed and actual dose. A prompt gamma-ray analysis system was developed for this purpose at the High Flux Reactor in Petten. The technique was compared with inductively coupled plasma-atomic emission spectrometry and showed good agreement. A substantial variation in 10 B clearance pattern after administration of borocaptate sodium was found between the different dogs. Consequently, the irradiation commencement was adjusted to the individually determined boron elimination curve. Mean blood- 10 B concentratios during irradiation of 25.8±2.2 μg/g (1 SD, n=18) and 49.3±5.3 μg/g (1 SD, n=17) were obtained for intended concentrations of 25 μg/g and 50 μg/g, respectively. These variations are a factor of two smaller than irradiations performed at a uniform post-infusion irradiation starting time. Such a careful bolld- 10 B monitoring procedure is a prerequisite for accurately obtaining such steep dose-response curves as observed during the dog study. (orig.)

Contrast-enhanced ultrasound imaging and in vivo circulatory kinetics with low-boiling-point nanoscale phase-change perfluorocarbon agents.

Science.gov (United States)

Sheeran, Paul S; Rojas, Juan D; Puett, Connor; Hjelmquist, Jordan; Arena, Christopher B; Dayton, Paul A

2015-03-01

Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published on the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low-boiling-point nanoscale PCCAs evaluated in vivo and compare data with those for conventional microbubbles with respect to contrast generation and circulation properties. To do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results indicate that droplets can produce contrast enhancement similar to that of microbubbles (7.29 to 18.24 dB over baseline, depending on formulation) and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also reports for the first time the ability to capture contrast washout kinetics of the target organ as a measure of vascular perfusion. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Capture of lipopolysaccharide (endotoxin) by the blood clot: a comparative study.

Science.gov (United States)

Armstrong, Margaret T; Rickles, Frederick R; Armstrong, Peter B

2013-01-01

In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot) and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse) operate to capture lipopolysaccharide (LPS, endotoxin). The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL) test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.

Capture of lipopolysaccharide (endotoxin by the blood clot: a comparative study.

Directory of Open Access Journals (Sweden)

Margaret T Armstrong

Full Text Available In vertebrates and arthropods, blood clotting involves the establishment of a plug of aggregated thrombocytes (the cellular clot and an extracellular fibrillar clot formed by the polymerization of the structural protein of the clot, which is fibrin in mammals, plasma lipoprotein in crustaceans, and coagulin in the horseshoe crab, Limulus polyphemus. Both elements of the clot function to staunch bleeding. Additionally, the extracellular clot functions as an agent of the innate immune system by providing a passive anti-microbial barrier and microbial entrapment device, which functions directly at the site of wounds to the integument. Here we show that, in addition to these passive functions in immunity, the plasma lipoprotein clot of lobster, the coagulin clot of Limulus, and both the platelet thrombus and the fibrin clot of mammals (human, mouse operate to capture lipopolysaccharide (LPS, endotoxin. The lipid A core of LPS is the principal agent of gram-negative septicemia, which is responsible for more than 100,000 human deaths annually in the United States and is similarly toxic to arthropods. Quantification using the Limulus Amebocyte Lysate (LAL test shows that clots capture significant quantities of LPS and fluorescent-labeled LPS can be seen by microscopy to decorate the clot fibrils. Thrombi generated in the living mouse accumulate LPS in vivo. It is suggested that capture of LPS released from gram-negative bacteria entrapped by the blood clot operates to protect against the disease that might be caused by its systemic dispersal.

Nedaplatin as a Single-Agent Chemotherapy May Support Palliative Therapy for Patients with Adenoid Cystic Carcinoma: A Case Report

Directory of Open Access Journals (Sweden)

Hiroyuki Hirakawa

2017-08-01

Full Text Available Adenoid cystic carcinoma (ACC is a rare form of adenocarcinoma, which is a broad term describing any cancer that begins in the glandular tissues. It can be found in the head and neck. We report a patient with recurrent ACC arising from the submandibular gland, treated with 100 mg/m2 nedaplatin every 4 weeks. Although our patient’s lactate dehydrogenase levels, which is produced by ACC, showed a rising trend throughout the treatment, the level decreased for approximately 2 weeks immediately after administration of nedaplatin every 4 weeks. Thus, there is a possibility that the agent may be effective. Complications such as anorexia and nausea were observed, but they were tolerated and manageable. Nedaplatin may be considered as a supportive agent during palliative therapy for patients with ACC. More clinical trials regarding nedaplatin are necessary, as this study may indicate that a medical approach works well for ACC.

Pilot clinical study of boron neutron capture therapy for recurrent hepatic cancer involving the intra-arterial injection of a (10)BSH-containing WOW emulsion.

Science.gov (United States)

Yanagie, Hironobu; Higashi, Syushi; Seguchi, Koji; Ikushima, Ichiro; Fujihara, Mituteru; Nonaka, Yasumasa; Oyama, Kazuyuki; Maruyama, Syoji; Hatae, Ryo; Suzuki, Minoru; Masunaga, Shin-ichiro; Kinashi, Tomoko; Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Narabayashi, Masaru; Kajiyama, Tetsuya; Maruhashi, Akira; Ono, Koji; Nakajima, Jun; Ono, Minoru; Takahashi, Hiroyuki; Eriguchi, Masazumi

2014-06-01

A 63-year-old man with multiple HCC in his left liver lobe was enrolled as the first patient in a pilot study of boron neutron capture therapy (BNCT) involving the selective intra-arterial infusion of a (10)BSH-containing water-in-oil-in-water emulsion ((10)BSH-WOW). The size of the tumorous region remained stable during the 3 months after the BNCT. No adverse effects of the BNCT were observed. The present results show that (10)BSH-WOW can be used as novel intra-arterial boron carriers during BNCT for HCC. Copyright © 2014 Elsevier Ltd. All rights reserved.

CCR 20th Anniversary Commentary: Immune-Related Response Criteria--Capturing Clinical Activity in Immuno-Oncology.

Science.gov (United States)

Hoos, Axel; Wolchok, Jedd D; Humphrey, Rachel W; Hodi, F Stephen

2015-11-15

To evaluate antitumor responses to chemotherapeutic agents, investigators would typically rely upon Response Evaluation Criteria in Solid Tumors (RECIST) or modified WHO criteria, which do not comprehensively capture responses with immunotherapeutic agents. In the December 1, 2009, issue of Clinical Cancer Research, Wolchok and colleagues reported their development of novel criteria, designated "Immune-related Response Criteria" (irRC), designed to better capture the response patterns observed with immunotherapies. Broad use of the irRC since then has allowed for a more comprehensive evaluation of immunotherapies in clinical trials, indicating that their concepts can be used in conjunction with either RECIST or WHO, and has shown irRC to be a powerful tool for improved clinical investigation. See related article by Wolchok et al., Clin Cancer Res 2009;15(23) December 1, 2009;7412-20. ©2015 American Association for Cancer Research.

Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

Science.gov (United States)

Sohn, Sang Kyun; Moon, Joon Ho

2015-08-01

According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluating Water Demand Using Agent-Based Modeling

Science.gov (United States)

Lowry, T. S.

2004-12-01

The supply and demand of water resources are functions of complex, inter-related systems including hydrology, climate, demographics, economics, and policy. To assess the safety and sustainability of water resources, planners often rely on complex numerical models that relate some or all of these systems using mathematical abstractions. The accuracy of these models relies on how well the abstractions capture the true nature of the systems interactions. Typically, these abstractions are based on analyses of observations and/or experiments that account only for the statistical mean behavior of each system. This limits the approach in two important ways: 1) It cannot capture cross-system disruptive events, such as major drought, significant policy change, or terrorist attack, and 2) it cannot resolve sub-system level responses. To overcome these limitations, we are developing an agent-based water resources model that includes the systems of hydrology, climate, demographics, economics, and policy, to examine water demand during normal and extraordinary conditions. Agent-based modeling (ABM) develops functional relationships between systems by modeling the interaction between individuals (agents), who behave according to a probabilistic set of rules. ABM is a "bottom-up" modeling approach in that it defines macro-system behavior by modeling the micro-behavior of individual agents. While each agent's behavior is often simple and predictable, the aggregate behavior of all agents in each system can be complex, unpredictable, and different than behaviors observed in mean-behavior models. Furthermore, the ABM approach creates a virtual laboratory where the effects of policy changes and/or extraordinary events can be simulated. Our model, which is based on the demographics and hydrology of the Middle Rio Grande Basin in the state of New Mexico, includes agent groups of residential, agricultural, and industrial users. Each agent within each group determines its water usage

Newer agents in antiplatelet therapy: a review

Directory of Open Access Journals (Sweden)

Yeung J

2012-06-01

Full Text Available Jennifer Yeung, Michael HolinstatCardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use due to variability in metabolism, time to onset, and reversibility. A focused effort in the development of newer antiplatelet therapies to address some of these shortcomings has resulted in a significant number of potential antiplatelet drugs which target enzymes (phosphodiesterase, cyclooxygenase, receptors (purinergic, prostaglandins, protease-activated receptors, thromboxane, and glycoproteins (αIIbß3, GPVI, vWF, GPIb in the platelet. The validation and search for newer antiplatelet therapeutic approaches proven to be superior to aspirin is still ongoing and should yield a better pharmacodynamic profile with fewer untoward side-effects to what is currently in use today.Keywords: platelet aggregation inhibitors, blood platelets, purinergic P2Y receptor antagonists, receptor, PAR-1, platelet glycoprotein GPIIb-IIIa, thrombosis

Development of local radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Lee, Seung Hoon; Lim, Sang Moo; Choi, Chang Woon; Chai, Jong Su; Kim, Eun Hee; Kim, Mi Sook; Yoo, Seong Yul; Cho, Chul Koo; Lee, Yong Sik; Lee, Hyun Moo

1999-04-01

The major limitations of radiation therapy for cancer are the low effectiveness of low LET and inevitable normal tissue damage. Boron Neutron Capture Therapy (BNCT) is a form of potent radiation therapy using Boron-10 having a high propensityof capturing theraml neutrons from nuclear reactor and reacting with a prompt nuclear reaction. Photodynamic therapy is a similiar treatment of modality to BNCT using tumor-seeking photosenistizer and LASER beam. If Boron-10 and photosensitizers are introduced selectively into tumor cells, it is theoretically possible to destroy the tumor and to spare the surrounding normal tissue. Therefore, BNCT and PDT will be new potent treatment modalities in the next century. In this project, we performed PDT in the patients with bladder cancers, oropharyngeal cancer, and skin cancers. Also we developed I-BPA, new porphyrin compounds, methods for estimation of radiobiological effect of neutron beam, and superficial animal brain tumor model. Furthermore, we prepared preclinical procedures for clinical application of BNCT, such as the macro- and microscopic dosimetry, obtaining thermal neutron flux from device used for fast neutron production in KCCH have been performed.

Development of local radiation therapy

International Nuclear Information System (INIS)

Lee, Seung Hoon; Lim, Sang Moo; Choi, Chang Woon; Chai, Jong Su; Kim, Eun Hee; Kim, Mi Sook; Yoo, Seong Yul; Cho, Chul Koo; Lee, Yong Sik; Lee, Hyun Moo

1999-04-01

The major limitations of radiation therapy for cancer are the low effectiveness of low LET and inevitable normal tissue damage. Boron Neutron Capture Therapy (BNCT) is a form of potent radiation therapy using Boron-10 having a high propensityof capturing theraml neutrons from nuclear reactor and reacting with a prompt nuclear reaction. Photodynamic therapy is a similiar treatment of modality to BNCT using tumor-seeking photosenistizer and LASER beam. If Boron-10 and photosensitizers are introduced selectively into tumor cells, it is theoretically possible to destroy the tumor and to spare the surrounding normal tissue. Therefore, BNCT and PDT will be new potent treatment modalities in the next century. In this project, we performed PDT in the patients with bladder cancers, oropharyngeal cancer, and skin cancers. Also we developed I-BPA, new porphyrin compounds, methods for estimation of radiobiological effect of neutron beam, and superficial animal brain tumor model. Furthermore, we prepared preclinical procedures for clinical application of BNCT, such as the macro- and microscopic dosimetry, obtaining thermal neutron flux from device used for fast neutron production in KCCH have been performed

Boron-Containing Compounds for Liposome-Mediated Tumor Localization and Application to Neutron Capture Therapy

International Nuclear Information System (INIS)

Hawthorne, M. Frederick

2005-01-01

Medical application of boron neutron capture therapy (BNCT) has been significantly hindered by the slow development of boron drug-targeting methodologies for the selective delivery of high boron concentration sto malignant cells. We have successfully sought to fill this need by creating liposomes suitable as in vivo boron delivery vehicles for BNCT. Delivery of therapeutic quantities of boron to tumors in murine models has been achieved with small unilamellar boron-rich liposomes. Subsequently, attempts have been made to improve delivery efficiency of liposomes encapsulating boron-containing water-soluble species into their hollow core by incorporating lipophilic boron compounds as addenda to the liposome bilayer, incorporating boron compounds as structural components of the bilayer (which however, poses the risk of sacrificing some stability), and combinations thereof. Regardless of the method, approximately 90% of the total liposome mass remains therapeutically inactive and comprised of the vehicle's construction materials, while less than 5% is boron for neutron targeting. Following this laboratory's intensive study, the observed tumor specificity of certain liposomes has been attributed to their diminutive size of these liposomes (30-150 nm), which enables these small vesicles to pass through the porous, immature vasculature of rapidly growing tumor tissue. We surmised that any amphiphilic nanoparticle of suitable size could possess some tumor selectivity. Consequently, the discovery of a very boron-rich nanoparticle delivery agent with biodistribution performance similar to unilamellar liposomes became one of our goals. Closomers, a new class of polyhedral borane derivatives, attracted us as an alternative BNCT drug-delivery system. We specifically envisioned dodeca (nido-carboranyl)-substituted closomers as possibly having a great potential role in BNCT drug delivery. They could function as extraordinarily boron-rich BNCT drugs since they are amphiphilic

Endocrine Therapy of Breast Cancer

National Research Council Canada - National Science Library

Clarke, Robert S

2005-01-01

...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., -40...

Biomedicines?Moving Biologic Agents into Approved Treatment Options

OpenAIRE

Cornetta, Kenneth

2013-01-01

The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and...

Endocrine Therapy of Breast Cancer

National Research Council Canada - National Science Library

Clarke, Robert

2008-01-01

...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

Endocrine Therapy of Breast Cancer

National Research Council Canada - National Science Library

Clarke, Robert

2007-01-01

...) or TAM should be given as first line endocrine therapy. Unfortunately, response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies, e.g., ̃40...

A virtual therapeutic environment with user projective agents.

Science.gov (United States)

Ookita, S Y; Tokuda, H

2001-02-01

Today, we see the Internet as more than just an information infrastructure, but a socializing place and a safe outlet of inner feelings. Many personalities develop aside from real world life due to its anonymous environment. Virtual world interactions are bringing about new psychological illnesses ranging from netaddiction to technostress, as well as online personality disorders and conflicts in multiple identities that exist in the virtual world. Presently, there are no standard therapy models for the virtual environment. There are very few therapeutic environments, or tools especially made for virtual therapeutic environments. The goal of our research is to provide the therapy model and middleware tools for psychologists to use in virtual therapeutic environments. We propose the Cyber Therapy Model, and Projective Agents, a tool used in the therapeutic environment. To evaluate the effectiveness of the tool, we created a prototype system, called the Virtual Group Counseling System, which is a therapeutic environment that allows the user to participate in group counseling through the eyes of their Projective Agent. Projective Agents inherit the user's personality traits. During the virtual group counseling, the user's Projective Agent interacts and collaborates to recover and increase their psychological growth. The prototype system provides a simulation environment where psychologists can adjust the parameters and customize their own simulation environment. The model and tool is a first attempt toward simulating online personalities that may exist only online, and provide data for observation.

Dosimetric analysis of BNCT - Boron Neutron Capture Therapy - coupled to 252Cf brachytherapy

International Nuclear Information System (INIS)

Brandao, Samia F.; Campos, Tarcisio P.R.

2009-01-01

The incidence of brain tumors is increasing in world population; however, the treatments employed in this type of tumor have a high rate of failure and in some cases have been considered palliative, depending on histology and staging of tumor. Its necessary to achieve the control tumor dose without the spread irradiation cause damage in the brain, affecting patient neurological function. Stereotactic radiosurgery is a technique that achieves this; nevertheless, other techniques that can be used on the brain tumor control must be developed, in order to guarantee lower dose on health surroundings tissues other techniques must be developing. The 252 Cf brachytherapy applied to brain tumors has already been suggested, showing promising results in comparison to photon source, since the active source is placed into the tumor, providing greater dose deposition, while more distant regions are spared. BNCT - Boron Neutron Capture Therapy - is another technique that is in developing to brain tumors control, showing theoretical superiority on the rules of conventional treatments, due to a selective irradiation of neoplasics cells, after the patient receives a borate compound infusion and be subjected to a epithermal neutrons beam. This work presents dosimetric studies of the coupling techniques: BNCT with 252 Cf brachytherapy, conducted through computer simulation in MCNP5 code, using a precise and well discretized voxel model of human head, which was incorporated a representative Glioblastoma Multiform tumor. The dosimetric results from MCNP5 code were exported to SISCODES program, which generated isodose curves representing absorbed dose rate in the brain. Isodose curves, neutron fluency, and dose components from BNCT and 252 Cf brachytherapy are presented in this paper. (author)

Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

Directory of Open Access Journals (Sweden)

Maia Hightower

Full Text Available Human immunodeficiency virus type 1 (HIV-1 and type 2 (HIV-2 are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

Theory and Practice of Positive Feminist Therapy: A Culturally Responsive Approach to Divorce Therapy with Chinese Women

Science.gov (United States)

Tzou, Jean Yuh-Jin; Kim, Eunha; Waldheim, Kim

2012-01-01

Positive Feminist Therapy (PFT) is a strength-based culturally responsive therapy model specifically designed for helping Chinese women facing marital conflicts and divorce, integrating Empowerment Feminist Therapy, systems theory, and positive psychology. To help clients become change agents, PFT uses clients' existing strengths to develop…

Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

NARCIS (Netherlands)

Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

2016-01-01

BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of

Novel agents in development for advanced non-small cell lung cancer.

Science.gov (United States)

Stinchcombe, Thomas E

2014-09-01

The identification of EGFR mutations and ALK rearrangements in nonsmall cell lung cancer (NSCLC) has led to the rapid development of targeted therapies and significant changes in the treatment paradigm. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and crizotinib are now standard therapies for patients with the appropriate molecular alteration. Current investigations are determining the mechanisms of resistance to targeted therapies and developing novel agents to combat resistance. For patients with KRAS mutant NSCLC, a phase III trial of the MEK inhibitor, selumetinib, has been initiated. For patients without a defined mutation or a mutation without a known targeted therapy, immunotherapy, ganetespib, nintedanib and MET inhibitors in combination with EGFR TKIs are in development. Preliminary results of phase III trials raise doubts about the future development of dacomitinib as a second-line agent.

Induction of chromosomal aberrations by neutron capture reactions

International Nuclear Information System (INIS)

Ikushima, Takaji

1993-01-01

Boron neutron capture reaction (B-NCR) has been practiced in the treatment of malignancies of the central nervous system and melanoma using a thermal neutron beam from the KUR. Because of the very large neutron absorption cross-section and high kinetic energy released, gadolinium (Gd-157) has been expected to be an another promising element for neutron capture therapy. The dose-response relationship was determined for the induction of chromosomal aberrations by neutron capture reactions by B-10 and Gd-157 in cultured mammalian cells. The cells were exposed to thermal neutron beam with and without B-10 enriched (97 atom %) boric acid or Gd-DTPA, and chromosome-type aberrations were analysed in the first metaphases following irradiation. The frequency of dicentrics and rings increased linearly with neutron fluence either in the presence or absence of B-10 boric acid, while the yield of chromosomal aberrations induced by Gd-NCR increased in a linear quadratic fashion as a function of dose as in γ-rayed cells. Survival curves for the cells exposed to thermal neutrons showed no shoulder irrespective of the loading of B-10, but Gd-NCR produced the survival curve with a small shoulder. The differential chromosomal response to B-NCR and Gd-NCR might reflect the difference in radiation quality generated from the two types of thermal neutron capture reaction. (J.P.N.)

Triple pulse shape discrimination and capture-gated spectroscopy in a composite heterogeneous scintillator

Energy Technology Data Exchange (ETDEWEB)

Sharma, M., E-mail: mksharma@umich.edu [University of Michigan, Ann Arbor, MI 48109 (United States); Nattress, J. [University of Michigan, Ann Arbor, MI 48109 (United States); Wilhelm, K. [Pennsylvania State University, University Park, PA 16802 (United States); Jovanovic, I. [University of Michigan, Ann Arbor, MI 48109 (United States)

2017-06-11

We demonstrate an all-solid-state design for a composite heterogeneous scintillation detector sensitive to interactions with high-energy photons (gammas), fast neutrons, and thermal neutrons. The scintillator exhibits triple pulse shape discrimination, effectively separating electron recoils, fast neutron recoils, and neutron captures. This is accomplished by combining the properties of two distinct scintillators, whereby a 51-mm diameter, 51-mm tall cylinder of pulse shape discriminating plastic is wrapped by a 320-µm thick sheet of {sup 6}LiF:ZnS(Ag), optically coupling the scintillators to each other and to the photomultiplier tube. In this way, the sensitivity to neutron captures is achieved without the need to load the plastic scintillator with a capture agent. We demonstrate a figure of merit of up to 1.2 for fast neutrons/gammas and 5.7 for thermal neutrons/gammas. Intrinsic capture efficiency is found to be 0.46±0.05% and is in good agreement with simulation, while gamma rejection was 10{sup −6} with respect to the capture region and 10{sup −4} with respect to the recoil region using a 300 keVee threshold. Finally, we show an improvement in capture-gated neutron spectroscopy by rejecting accidental gamma coincidences using pulse shape discrimination in the plastic scintillator.

A large animal model for boron neutron capture therapy

International Nuclear Information System (INIS)

Gavin, P.R.; Kraft, S.L.; DeHaan, C.E.; Moore, M.P.; Griebenow, M.L.

1992-01-01

An epithermal neutron beam is needed to treat relatively deep seated tumors. The scattering characteristics of neutrons in this energy range dictate that in vivo experiments be conducted in a large animal to prevent unacceptable total body irradiation. The canine species has proven an excellent model to evaluate the various problems of boron neutron capture utilizing an epithermal neutron beam. This paper discusses three major components of the authors study: (1) the pharmacokinetics of borocaptate sodium (NA 2 B 12 H 11 SH or BSH) in dogs with spontaneously occurring brain tumors, (2) the radiation tolerance of normal tissues in the dog using an epithermal beam alone and in combination with borocaptate sodium, and (3) initial treatment of dogs with spontaneously occurring brain tumors utilizing borocaptate sodium and an epithermal neutron beam

Targeted Therapies in Epithelial Ovarian Cancer

Directory of Open Access Journals (Sweden)

Jurjees Hasan

2010-02-01

Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Targeted Therapies in Epithelial Ovarian Cancer

Energy Technology Data Exchange (ETDEWEB)

Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

2010-02-23

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

A case of malignant hyperthermia captured by an anesthesia information management system.

Science.gov (United States)

Maile, Michael D; Patel, Rajesh A; Blum, James M; Tremper, Kevin K

2011-04-01

Many cases of malignant hyperthermia triggered by volatile anesthetic agents have been described. However, to our knowledge, there has not been a report describing the precise changes in physiologic data of a human suffering from this process. Here we describe a case of malignant hyperthermia in which monitoring information was frequently and accurately captured by an anesthesia information management system.

Non-carrier-added 186,188Re labeled 17α-ethynylestradiol: a potential breast cancer imaging and therapy agent

International Nuclear Information System (INIS)

Fassbender, M.E.; Phillips, Dennis R.; Peterson, E.J.; Ott, K.C.; Arterburn, J.B.

2001-01-01

Receptor-targeted radiopharmaceuticals constitute potential agents for the diagnosis and therapy of cancer. Breast cancer is the most prevalent form of diagnosed cancer in women in the United States, and it accounts for the second highest number of cases of cancer fatalities (1). In Approximately two-thirds of the breast tumors, estrogen and progesterone steroid hormone receptors can be found. Such tumors can often be treated successfully with anti-estrogen hormone therapy (2). Hence, the ability to determine the estrogen receptor (ER) contend of the breast tumor is essential for making the most appropriate choice of treatment for the patient. Along with this diagnostic aspect, steroid-based radiopharmaceuticals with high specific activity offer an encouraging prospect for therapeutic applications: 186,188 Re labeled steroids binding to receptors expressed by cancer cells appear to be potential agents for the irradiation of small to medium-sized tumors. 186 Re has been regarded as an ideal radionuclide for radiotherapy due to its appropriate half-live of 90 h and β-energy of 1.07 MeV. Moreover, the γ-emission of 137 keV that allows in vivo imaging while in therapy is an additional bonus. 188 Re is obtained from a 188 W/ 188 Re radionuclide generator system, representing an advantage for availability at radiopharmacy laboratory by daily elution. In addition, 188 Re emits high energy beta particles with an average energy of 769 keV, and the emission of the 155 keV allows simultaneous imaging for biodistribution evaluation in vivo. In order to avoid competitive saturation of the binding sites of the ligand receptor, Re labeled steroids with high specific activity are required, and the removal of all excess unlabeled ligands is mandatory. 188 Re is eluted from a 188 W/ 188 Re generator produced and provided by Oak Ridge National Laboratory (3). This paper outlines the solid phase-supported preparation of an n.c.a. ( 188 Re)Re-imido estradiol compound. The

User's manual of a supporting system for treatment planning in boron neutron capture therapy. JAERI computational dosimetry system

CERN Document Server

Kumada, H

2002-01-01

A boron neutron capture therapy (BNCT) with epithermal neutron beam is expected to treat effectively for malignant tumor that is located deeply in the brain. It is indispensable to estimate preliminarily the irradiation dose in the brain of a patient in order to perform the epithermal neutron beam BNCT. Thus, the JAERI Computational Dosimetry System (JCDS), which can calculate the dose distributions in the brain, has been developed. JCDS is a software that creates a 3-dimensional head model of a patient by using CT and MRI images and that generates a input data file automatically for calculation neutron flux and gamma-ray dose distribution in the brain by the Monte Carlo code: MCNP, and that displays the dose distribution on the head model for dosimetry by using the MCNP calculation results. JCDS has any advantages as follows; By treating CT data and MRI data which are medical images, a detail three-dimensional model of patient's head is able to be made easily. The three-dimensional head image is editable to ...

Update on smoking cessation therapies.

LENUS (Irish Health Repository)

Glynn, Deirdre A

2009-04-01

As a reflection of an exponential increase in smoking rates throughout the world during the last century, the economic and human burden of mortality and morbidity related to smoking is now clearly defined. Smoking cessation is associated with health benefits for people of all ages. In this paper we provide a comprehensive review of current licensed pharmacological smoking cessation agents including efficacy and safety profiles, with comparisons of individual therapies available. Furthermore, we offer a prospective on the need for further testing of other agents including novel avenues of therapy.

Rapid discovery of peptide capture candidates with demonstrated specificity for structurally similar toxins

Science.gov (United States)

Sarkes, Deborah A.; Hurley, Margaret M.; Coppock, Matthew B.; Farrell, Mikella E.; Pellegrino, Paul M.; Stratis-Cullum, Dimitra N.

2016-05-01

Peptides have emerged as viable alternatives to antibodies for molecular-based sensing due to their similarity in recognition ability despite their relative structural simplicity. Various methods for peptide capture reagent discovery exist, including phage display, yeast display, and bacterial display. One of the primary advantages of peptide discovery by bacterial display technology is the speed to candidate peptide capture agent, due to both rapid growth of bacteria and direct utilization of the sorted cells displaying each individual peptide for the subsequent round of biopanning. We have previously isolated peptide affinity reagents towards protective antigen of Bacillus anthracis using a commercially available automated magnetic sorting platform with improved enrichment as compared to manual magnetic sorting. In this work, we focus on adapting our automated biopanning method to a more challenging sort, to demonstrate the specificity possible with peptide capture agents. This was achieved using non-toxic, recombinant variants of ricin and abrin, RiVax and abrax, respectively, which are structurally similar Type II ribosomal inactivating proteins with significant sequence homology. After only two rounds of biopanning, enrichment of peptide capture candidates binding abrax but not RiVax was achieved as demonstrated by Fluorescence Activated Cell Sorting (FACS) studies. Further sorting optimization included negative sorting against RiVax, proper selection of autoMACS programs for specific sorting rounds, and using freshly made buffer and freshly thawed protein target for each round of biopanning for continued enrichment over all four rounds. Most of the resulting candidates from biopanning for abrax binding peptides were able to bind abrax but not RiVax, demonstrating that short peptide sequences can be highly specific even at this early discovery stage.

A novel single walled carbon nanotube (SWCNT) functionalization agent facilitating in vivo combined chemo/thermo therapy

Science.gov (United States)

Zhang, Liwen; Rong, Pengfei; Chen, Minglong; Gao, Shi; Zhu, Lei

2015-10-01

Carbon nanotubes (CNTs) have shown intriguing applications in biotechnological and biomedical fields due to their unique shape and properties. However, the fact that unmodified CNTs are prone to aggregation, stunts CNTs applications under physiological conditions. In this research, we found that as little as 1/5th the single walled carbon nanotube (SWCNT) weight of Evans Blue (EB) is capable of dispersing SWCNT as well as facilitating SWCNT functionalization. In view of the binding between EB and albumin, the yielding product (SWCNT/EB) demonstrated extreme stability for weeks under physiological conditions and it can be endowed with a therapeutic ability by simply mixing SWCNT/EB with an albumin based drug. Specifically, the formed SWCNT/EB/albumin/PTX nanocomplex exhibits strong near-infrared (NIR) absorbance, and can serve as an agent for chemo/thermal therapeutic purposes. Our in vivo result reveals that SWCNT/EB/albumin/PTX after being administered into the MDA-MB-435 tumor would effectively ablate the tumor by chemo and photothermal therapy. Such a combined treatment strategy provides remarkable therapeutic outcomes in restraining tumor growth compared to chemo or photothermal therapy alone. Overall, our strategy of dispersing SWCNTs by EB can be used as a platform for carrying other drugs or functional genes with the aid of albumin to treat diseases. The present study opens new opportunities in surface modification of SWCNTs for future clinical disease treatment.Carbon nanotubes (CNTs) have shown intriguing applications in biotechnological and biomedical fields due to their unique shape and properties. However, the fact that unmodified CNTs are prone to aggregation, stunts CNTs applications under physiological conditions. In this research, we found that as little as 1/5th the single walled carbon nanotube (SWCNT) weight of Evans Blue (EB) is capable of dispersing SWCNT as well as facilitating SWCNT functionalization. In view of the binding between EB and

CO 2 Capture from Dilute Gases as a Component of Modern Global Carbon Management

KAUST Repository

Jones, Christopher W.

2011-01-01

The growing atmospheric CO2 concentration and its impact on climate have motivated widespread research and development aimed at slowing or stemming anthropogenic carbon emissions. Technologies for carbon capture and sequestration (CCS) employing mass separating agents that extract and purify CO2 from flue gas emanating from large point sources such as fossil fuel-fired electricity-generating power plants are under development. Recent advances in solvents, adsorbents, and membranes for postcombust- ion CO 2 capture are described here. Specifically, room-temperature ionic liquids, supported amine materials, mixed matrix and facilitated transport membranes, and metal-organic framework materials are highlighted. In addition, the concept of extracting CO2 directly from ambient air (air capture) as a means of reducing the global atmospheric CO2 concentration is reviewed. For both conventional CCS from large point sources and air capture, critical research needs are identified and discussed. © Copyright 2011 by Annual Reviews. All rights reserved.

CO 2 Capture from Dilute Gases as a Component of Modern Global Carbon Management

KAUST Repository

Jones, Christopher W.

2011-07-15

The growing atmospheric CO2 concentration and its impact on climate have motivated widespread research and development aimed at slowing or stemming anthropogenic carbon emissions. Technologies for carbon capture and sequestration (CCS) employing mass separating agents that extract and purify CO2 from flue gas emanating from large point sources such as fossil fuel-fired electricity-generating power plants are under development. Recent advances in solvents, adsorbents, and membranes for postcombust- ion CO 2 capture are described here. Specifically, room-temperature ionic liquids, supported amine materials, mixed matrix and facilitated transport membranes, and metal-organic framework materials are highlighted. In addition, the concept of extracting CO2 directly from ambient air (air capture) as a means of reducing the global atmospheric CO2 concentration is reviewed. For both conventional CCS from large point sources and air capture, critical research needs are identified and discussed. © Copyright 2011 by Annual Reviews. All rights reserved.

Introducing a logic for real-world agents with degrees of belief

CSIR Research Space (South Africa)

Rens, GB

2009-12-01

Full Text Available stream_source_info Gens_2009.pdf.txt stream_content_type text/plain stream_size 3189 Content-Encoding UTF-8 stream_name Gens_2009.pdf.txt Content-Type text/plain; charset=UTF-8 Introducing a Logic for Real-world Agents... the world could be. A further step to capture uncertain knowledge is to assign a likelihood to each state considered possible so that degrees of belief can be captured. Now as the robot acts and observes while completing its tasks, it will change its...

Molecular profiling of childhood cancer: Biomarkers and novel therapies.

Science.gov (United States)

Saletta, Federica; Wadham, Carol; Ziegler, David S; Marshall, Glenn M; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D; Byrne, Jennifer A

2014-06-01

Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

Anti-ischemic effects of inotropic agents in experimental right ventricular infarction.

NARCIS (Netherlands)

Hein, M.; Roehl, A.B.; Baumert, J.H.; Scherer, K.; Steendijk, P.; Rossaint, R.

2009-01-01

BACKGROUND: Right ventricular (RV) function is an important determinant of survival after myocardial infarction. The efficacy of reperfusion therapy might be increased by the cardioprotective action of inotropic agents, which are used for symptomatic therapy in situations with compromised

Evolution of and perspectives on therapeutic approaches to nerve agent poisoning.

Science.gov (United States)

Masson, Patrick

2011-09-25

After more than 70 years of considerable efforts, research on medical defense against nerve agents has come to a standstill. Major progress in medical countermeasures was achieved between the 50s and 70s with the development of anticholinergic drugs and carbamate-based pretreatment, the introduction of pyridinium oximes as antidotes, and benzodiazepines in emergency treatments. These drugs ensure good protection of the peripheral nervous system and mitigate the acute effects of exposure to lethal doses of nerve agents. However, pyridostigmine and cholinesterase reactivators currently used in the armed forces do not protect/reactivate central acetylcholinesterases. Moreover, other drugs used are not sufficiently effective in protecting the central nervous system against seizures, irreversible brain damages and long-term sequelae of nerve agent poisoning.New developments of medical counter-measures focus on: (a) detoxification of organophosphorus molecules before they react with acetylcholinesterase and other physiological targets by administration of stoichiometric or catalytic scavengers; (b) protection and reactivation of central acetylcholinesterases, and (c) improvement of neuroprotection following delayed therapy.Future developments will aim at treatment of acute and long-term effects of low level exposure to nerve agents, research on alternative routes for optimizing drug delivery, and therapies. Though gene therapy for in situ generation of bioscavengers, and cell therapy based on neural progenitor engraftment for neuronal regeneration have been successfully explored, more studies are needed before practical medical applications can be made of these new approaches. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Agent-Based Modeling for Testing and Designing Novel Decentralized Command and Control System Paradigms

National Research Council Canada - National Science Library

Bonabeau, Eric; Hunt, Carl W; Gaudiano, Paolo

2003-01-01

Agent-based modeling (ABM) is a recent simulation modeling technique that consists of modeling a system from the bottom up, capturing the interactions taking place between the system's constituent units...

Dose distribution and clinical response of glioblastoma treated with boron neutron capture therapy

Energy Technology Data Exchange (ETDEWEB)

Matsuda, M. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan)], E-mail: mhide-m@gk9.so-net.ne.jp; Yamamoto, T. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan); Kumada, H. [Japan Atomic Energy Agency, Shirakatashirane 2-4, Tokai (Japan); Nakai, K.; Shirakawa, M.; Tsurubuchi, T.; Matsumura, A. [Department of Neurosurgery, Graduate School of Comprehensive Human Science, University of Tsukuba, Tennodai 1-1-1, Tsukuba (Japan)

2009-07-15

The dose distribution and failure pattern after treatment with the external beam boron neutron capture therapy (BNCT) protocol were retrospectively analyzed. BSH (5 g/body) and BPA (250 mg/kg) based BNCT was performed in eight patients with newly diagnosed glioblastoma. The gross tumor volume (GTV) and clinical target volume (CTV)-1 were defined as the residual gadolinium-enhancing volume. CTV-2 and CTV-3 were defined as GTV plus a margin of 2 and 3 cm, respectively. As additional photon irradiation, a total X-ray dose of 30 Gy was given to the T2 high intensity area on MRI. Five of the eight patients were alive at analysis for a mean follow-up time of 20.3 months. The post-operative median survival time of the eight patients was 27.9 months (95% CI=21.0-34.8). The minimum tumor dose of GTV, CTV-2, and CTV-3 averaged 29.8{+-}9.9, 15.1{+-}5.4, and 12.4{+-}2.9 Gy, respectively. The minimum tumor non-boron dose of GTV, CTV-2, and CTV-3 averaged 2.0{+-}0.5, 1.3{+-}0.3, and 1.1{+-}0.2 Gy, respectively. The maximum normal brain dose, skin dose, and average brain dose were 11.4{+-}1.5, 9.6{+-}1.4, and 3.1{+-}0.4 Gy, respectively. The mean minimum dose at the failure site in cases of in-field recurrence (IR) and out-field recurrence (OR) was 26.3{+-}16.7 and 14.9 GyEq, respectively. The calculated doses at the failure site were at least equal to the tumor control doses which were previously reported. We speculate that the failure pattern was related to an inadequate distribution of boron-10. Further improvement of the microdistribution of boron compounds is expected, and may improve the tumor control by BNCT.

Radiological protection considerations during the treatment of glioblastoma patients by boron neutron capture therapy at the high flux reactor in Petten, The Netherlands

International Nuclear Information System (INIS)

Moss, R.L.; Rassow, J.; Finke, E.; Sauerwein, W.; Stecher-Rasmussen, F.

2001-01-01

A clinical trial of Boron Neutron Capture Therapy (BNCT) for glioblastoma patients has been in progress at the High Flux Reactor (HFR) at Petten since October 1997. The JRC (as licence holder of the HFR) must ensure that radiological protection measures are provided. The BNCT trial is a truly European trial, whereby the treatment takes place at a facility in the Netherlands under the responsibility of clinicians from Germany and patients are treated from several European countries. Consequently, radiological protection measures satisfy both German and Dutch laws. To respect both laws, a BNCT radioprotection committee was formed under the chairmanship of an independent radioprotection expert, with members representing all disciplines in the trial. A special nuance of BNCT is that the radiation is provided by a mixed neutron/gamma beam. The radiation dose to the patient is thus a complex mix due to neutrons, gammas and neutron capture in boron, nitrogen and hydrogen, which, amongst others, need to be correctly calculated in non-commercial and validated treatment planning codes. Furthermore, due to neutron activation, measurements on the patient are taken regularly after treatment. Further investigations along these lines include dose determination using TLDs and boron distribution measurements using on-line gamma ray spectroscopy. (author)

Hydrogen fluoride capture by imidazolium acetate ionic liquid

Science.gov (United States)

Chaban, Vitaly

2015-04-01

Extraction of hydrofluoric acid (HF) from oils is a drastically important problem in petroleum industry, since HF causes quick corrosion of pipe lines and brings severe health problems to humanity. Some ionic liquids (ILs) constitute promising scavenger agents thanks to strong binding to polar compounds and tunability. PM7-MD simulations and hybrid density functional theory are employed here to consider HF capture ability of ILs. Discussing the effects and impacts of the cation and the anion separately and together, we evaluate performance of imidazolium acetate and outline systematic search guidelines for efficient adsorption and extraction of HF.

Recurrent squamous cell carcinoma of the skin treated successfully with single agent cetuximab therapy

Directory of Open Access Journals (Sweden)

Seber S

2016-02-01

Full Text Available Selcuk Seber,1 Aylin Gonultas,2 Ozlem Ozturk,2 Tarkan Yetisyigit1 1Department of Medical Oncology, Faculty of Medicine, Namik Kemal University, 2Pathology Department, Tekirdag State Hospital, Tekirdag, Turkey Abstract: Recurrent squamous cell carcinoma of the skin is a rare but difficult to treat condition. Frequently, the disease presents itself in elderly patients with poor performance status and bearing many comorbidities, thus the decision to administer systemic chemotherapy becomes difficult to make. In addition, current chemotherapeutic protocols response rates are far from satisfactory. Recently cetuximab, a chimeric antibody against epidermal growth factor receptor, is increasingly being reported as an alternative treatment. We therefore report this case of a recurrent squamous cell carcinoma of the skin in an elderly woman with poor performance status and who had an excellent clinical response to single agent cetuximab therapy with complete resolution of the disease and minimal toxicity during the course of the treatment to provide evidence for future prospective clinical trials. Keywords: cetuximab, EGFR inhibiton, squamous cell carcinoma of the skin

Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

Science.gov (United States)

Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

2013-01-01

Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

Nanoscale theranostics for physical stimulus-responsive cancer therapies.

Science.gov (United States)

Chen, Qian; Ke, Hengte; Dai, Zhifei; Liu, Zhuang

2015-12-01

Physical stimulus-responsive therapies often employing multifunctional theranostic agents responsive to external physical stimuli such as light, magnetic field, ultra-sound, radiofrequency, X-ray, etc., have been widely explored as novel cancer therapy strategies, showing encouraging results in many pre-clinical animal experiments. Unlike conventional cancer chemotherapy which often accompanies with severe toxic side effects, physical stimulus-responsive agents usually are non-toxic by themselves and would destruct cancer cells only under specific external stimuli, and thus could offer greatly reduced toxicity and enhanced treatment specificity. In addition, physical stimulus-responsive therapies can also be combined with other traditional therapeutics to achieve synergistic anti-tumor effects via a variety of mechanisms. In this review, we will summarize the latest progress in the development of physical stimulus-responsive therapies, and discuss the important roles of nanoscale theranostic agents involved in those non-conventional therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacologic therapy for acute pancreatitis

Science.gov (United States)

Kambhampati, Swetha; Park, Walter; Habtezion, Aida

2014-01-01

While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

Design of experiment existing parameter physics for supporting of Boron Neutron Capture Therapy (BNCT) method a t the piercing radial beam port of Kartini research reactor

International Nuclear Information System (INIS)

Indry Septiana Novitasari; Yosaphat Sumardi; Widarto

2014-01-01

The experiment existing parameters physics for supporting of in vivo and in vitro test facility of Boron Neutron Capture Therapy (BNCT) preliminary study at the piercing radial beam port has been done. The existing experiments is needed for determining that the parameter physics is fulfill the BNCT method requirement. To realize the existing experiment have been done by design analysis, methodology, calculation method and some procedure related with radiation safety analysis and environment. Preparation for existing experiment physics such as foil detector of Gold (Au) should be irradiated for 30 minute, irradiation instrument and procedure related with the experiment for radiation safety. (author)

Amino acid salt solutions as solvents in CO2 capture from flue gas

DEFF Research Database (Denmark)

Lerche, Benedicte Mai; Thomsen, Kaj; Stenby, Erling Halfdan

New solvents based on the salts of amino acids have emerged as an alternative to the alkanolamine solutions, for the chemical absorption of CO2 from flue gas. But only few studies on amino acids as CO2 capturing agents have been performed so far. One of the interesting features of amino acid salt...... solutions is their ability to form solid precipitates upon the absorption of CO2. The occurrence of crystallization offers the possibility of increasing the CO2 loading capacity of the solvent. However, precipitation can also have negative effect on the CO2 capture process. The chemical nature of the solid...... of glycine, taurine, and lysine, while in the case of proline, and glutamic acid, the precipitate was found to be bicarbonate. These results give an important contribution to further understanding the potential of amino acid salt solutions in CO2 capture from flue gas....

FiR 1 reactor in service for boron neutron capture therapy (BNCT) and isotope production

International Nuclear Information System (INIS)

Auterinen, I.; Salmenhaara, S.E.J. . Author

2004-01-01

The FiR 1 reactor, a 250 kW Triga reactor, has been in operation since 1962. The main purpose for the existence of the reactor is now the Boron Neutron Capture Therapy (BNCT), but FiR 1 has also an important national role in providing local enterprises and research institutions in the fields of industrial measurements, pharmaceuticals, electronics etc. with isotope production and activation analysis services. In the 1990's a BNCT treatment facility was built at the FiR 1 reactor located at Technical Research Centre of Finland. A special new neutron moderator material Fluental TM (Al+AlF3+Li) developed at VTT ensures the superior quality of the neutron beam. Also the treatment environment is of world top quality after a major renovation of the whole reactor building in 1997. Recently the lithiated polyethylene neutron shielding of the beam aperture was modified to ease the positioning of the patient close to the beam aperture. Increasing the reactor power to 500 kW would allow positioning of the patient further away from the beam aperture. Possibilities to accomplish a safety analysis for this is currently under considerations. Over thirty patients have been treated at FiR 1 since May 1999, when the license for patient treatment was granted to the responsible BNCT treatment organization, Boneca Corporation. Currently three clinical trial protocols for tumours in the brain as well as in the head and neck region are recruiting patients. (author)

Development of a new anti-cancer agent for targeted radionuclide therapy: β- radiolabeled RAFT-RGD

International Nuclear Information System (INIS)

Petitprin, A.

2013-01-01

β-emitters radiolabeled RAFT-RGD as new agents for internal targeted radiotherapy. The αvβ3 integrin is known to play an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. Because of its overexpression on neo-endothelial cells such as those present in growing tumors, as well as on tumor cells of various origins, αvβ3 integrin is an attractive molecular target for diagnosis and therapy of the rapidly growing and metastatic tumors. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin αvβ3 in vitro and in vivo. RAFT-RGD has been used for tumor imaging and drug targeting. This study is the first to evaluate the therapeutic potential of the β-emitters radiolabeled tetrameric RGD peptide RAFT-RGD in a Nude mouse model of αvβ3 -expressing tumors. An injection of 37 MBq of 90 Y-RAFT-RGD or 177 Lu-RAFT-RGD in mice with αvβ3 -positive tumors caused a significant growth delay as compared with mice treated with 37 MBq of 90 Y-RAFT-RAD or 177 Lu-RAFT-RAD or untreated mice. In comparison, an injection of 30 MBq of 90 Y-RAFT-RGD had no efficacy for the treatment of αvβ3 -negative tumors. 90 Y-RAFT-RGD and 177 Lu-RAFT-RGD are potent αvβ3 -expressing tumor targeting agents for internal targeted radiotherapy. (author)

A benefit-risk assessment of class III antiarrhythmic agents

DEFF Research Database (Denmark)

Elming, Hanne; Brendorp, Bente; Pehrson, Steen

2004-01-01

The prevalence of arrhythmia in the population is increasing as more people survive for longer with cardiovascular disease. It was once thought that antiarrhythmic therapy could save life, however, it is now evident that antiarrhythmic therapy should be administrated with the purpose of symptomat......, and reducing the need for implantable cardioverter defibrillator shock/antitachycardia therapy, since no class III antiarrhythmic agents have proven survival benefit. The risks discussed mainly focus on pro-arrhythmia as torsade de pointes ventricular tachycardia....

Intelligent judgements over health risks in a spatial agent-based model.

Science.gov (United States)

Abdulkareem, Shaheen A; Augustijn, Ellen-Wien; Mustafa, Yaseen T; Filatova, Tatiana

2018-03-20

Millions of people worldwide are exposed to deadly infectious diseases on a regular basis. Breaking news of the Zika outbreak for instance, made it to the main media titles internationally. Perceiving disease risks motivate people to adapt their behavior toward a safer and more protective lifestyle. Computational science is instrumental in exploring patterns of disease spread emerging from many individual decisions and interactions among agents and their environment by means of agent-based models. Yet, current disease models rarely consider simulating dynamics in risk perception and its impact on the adaptive protective behavior. Social sciences offer insights into individual risk perception and corresponding protective actions, while machine learning provides algorithms and methods to capture these learning processes. This article presents an innovative approach to extend agent-based disease models by capturing behavioral aspects of decision-making in a risky context using machine learning techniques. We illustrate it with a case of cholera in Kumasi, Ghana, accounting for spatial and social risk factors that affect intelligent behavior and corresponding disease incidents. The results of computational experiments comparing intelligent with zero-intelligent representations of agents in a spatial disease agent-based model are discussed. We present a spatial disease agent-based model (ABM) with agents' behavior grounded in Protection Motivation Theory. Spatial and temporal patterns of disease diffusion among zero-intelligent agents are compared to those produced by a population of intelligent agents. Two Bayesian Networks (BNs) designed and coded using R and are further integrated with the NetLogo-based Cholera ABM. The first is a one-tier BN1 (only risk perception), the second is a two-tier BN2 (risk and coping behavior). We run three experiments (zero-intelligent agents, BN1 intelligence and BN2 intelligence) and report the results per experiment in terms of

Maintenance therapy in advanced non-small cell lung cancer: current status and future implications.

Science.gov (United States)

Stinchcombe, Thomas E; Socinski, Mark A

2011-01-01

Maintenance therapy for patients with advanced non-small cell lung cancer has been an area of intense investigation. Maintenance therapy has been divided into two broad categories: continuation maintenance when the chemotherapy or targeted agent was part of a defined number of cycles of combination therapy and in the absence of disease progression is continued as a single agent or switch maintenance when a third agent is initiated after four cycles of platinum-based double-agent chemotherapy in the absence of disease progression. Two monoclonal antibodies, cetuximab and bevacizumab, are used as continuation maintenance, but the incremental benefit of the maintenance therapy with these agents is undetermined. Phase III trials have not revealed an overall survival benefit for continuation maintenance chemotherapy, and this approach should be considered investigational. Phase III trials have demonstrated an improvement in overall survival with switch maintenance therapy with pemetrexed compared with placebo in patients with nonsquamous histology and erlotinib compared with placebo. Phase III trials have not revealed an improvement in quality of life with maintenance therapy. In the trials of maintenance therapy, 30 to 40% of patients enrolled in the observation or placebo arm did not receive second-line therapy, and among the patients who did receive second-line therapy, there was significant heterogeneity in the therapy. The development of maintenance therapy has raised issues about the role of treatment-free intervals in routine clinical care, trial design issues such as the optimal endpoint, the ethics of a placebo arm, and the implications of maintenance therapy for first-line trials.

Chelating agents in pharmacology, toxicology and therapeutics

International Nuclear Information System (INIS)

1988-01-01

The proceedings contain 71 abstracts of papers. Fourteen abstracts were inputted in INIS. The topics covered include: the effects of chelating agents on the retention of 63 Ni, 109 Cd, 203 Hg, 144 Ce, 95 Nb and the excretion of 210 Po, 63 Ni, 48 V, 239 Pu, 241 Am, 54 Mn; the applications of tracer techniques for studies of the efficacy of chelation therapy in patients with heart and brain disorders; and the treatment of metal poisoning with chelating agents. (J.P.)

The Role of Implicit Motives in Strategic Decision-Making: Computational Models of Motivated Learning and the Evolution of Motivated Agents

Directory of Open Access Journals (Sweden)

Kathryn Merrick

2015-11-01

Full Text Available Individual behavioral differences in humans have been linked to measurable differences in their mental activities, including differences in their implicit motives. In humans, individual differences in the strength of motives such as power, achievement and affiliation have been shown to have a significant impact on behavior in social dilemma games and during other kinds of strategic interactions. This paper presents agent-based computational models of power-, achievement- and affiliation-motivated individuals engaged in game-play. The first model captures learning by motivated agents during strategic interactions. The second model captures the evolution of a society of motivated agents. It is demonstrated that misperception, when it is a result of motivation, causes agents with different motives to play a given game differently. When motivated agents who misperceive a game are present in a population, higher explicit payoff can result for the population as a whole. The implications of these results are discussed, both for modeling human behavior and for designing artificial agents with certain salient behavioral characteristics.

Chelation Therapy for Mercury Poisoning

OpenAIRE

Rong Guan; Han Dai

2009-01-01

Chelation therapy has been the major treatment for heavy metal poisoning. Various chelating agents have been developed and tested for treatment of heavy metal intoxications, including mercury poisoning. It has been clearly shown that chelating agents could rescue the toxicity caused by heavy metal intoxication, but the potential preventive role of chelating agents against heavy metal poisoning has not been explored much. Recent paper by Siddiqi and colleagues has suggested a protective role o...

A Distributed Framework for Real Time Path Planning in Practical Multi-agent Systems

KAUST Repository

Abdelkader, Mohamed; Jaleel, Hassan; Shamma, Jeff S.

2017-01-01

We present a framework for distributed, energy efficient, and real time implementable algorithms for path planning in multi-agent systems. The proposed framework is presented in the context of a motivating example of capture the flag which

CASCADE: An Agent Based Framework For Modeling The Dynamics Of Smart Electricity Systems

OpenAIRE

Rylatt, R. M.; Gammon, Rupert; Boait, Peter John; Varga, L.; Allen, P.; Savill, M.; Snape, J. Richard; Lemon, Mark; Ardestani, B. M.; Pakka, V. H.; Fletcher, G.; Smith, S.; Fan, D.; Strathern, M.

2013-01-01

Collaborative project with Cranfield University The Complex Adaptive Systems, Cognitive Agents and Distributed Energy (CASCADE) project is developing a framework based on Agent Based Modelling (ABM). The CASCADE Framework can be used both to gain policy and industry relevant insights into the smart grid concept itself and as a platform to design and test distributed ICT solutions for smart grid based business entities. ABM is used to capture the behaviors of diff erent socia...

Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation.

Science.gov (United States)

Martinez de Pinillos Bayona, Alejandra; Moore, Caroline M; Loizidou, Marilena; MacRobert, Alexander J; Woodhams, Josephine H

2016-03-01

Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI-based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

A short history of anti-rheumatic therapy - VII. Biological agents

Directory of Open Access Journals (Sweden)

B. Gatto

2011-11-01

Full Text Available The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy

International Nuclear Information System (INIS)

Goodman, J.H.; McGregor, J.M.; Clendenon, N.R.; Gahbauer, R.A.; Barth, R.F.; Soloway, A.H.; Fairchild, R.G.

1990-01-01

This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity

Meeting the challenge of homogenous boron targeting of heterogeneous tumors for effective boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Heber, Elisa M.; Trivillin, Veronica A.; Itoiz, Maria E.; Rebagliati, J. Raul; Batistoni, Daniel; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.; Gonzalez, Beatriz N.

2006-01-01

BNCT is a tumor cell targeted radiation therapy. Inadequately boron targeted tumor populations jeopardize tumor control. Meeting the to date unresolved challenge of homogeneous targeting of heterogeneous tumors with effective boron carriers would contribute to therapeutic efficacy. The aim of the present study was to evaluate the degree of variation in boron content delivered by boronophenylalanine (BPA), GB-10 (Na 2 10 B 10 H 10 ) and the combined administration of (BPA+GB-10) in different portions of tumor, precancerous tissue around tumor and normal pouch tissue in the hamster cheek pouch oral cancer model. Boron content was evaluated by ICP-AES. The degree of homogeneity in boron targeting was assessed in terms of the coefficient of variation ([S.D./Mean]x100) of boron values. Statistical analysis of the results was performed by one-way ANOVA and the least significant difference test. GB-10 and GB-10 plus BPA achieved respectively a statistically significant 1.8-fold and 3.3-fold increase in targeting homogeneity over BPA. The combined boron compound administration protocol contributes to homogeneous targeting of heterogeneous tumors and would increase therapeutic efficacy of BNCT by exposing all tumor populations to neutron capture reactions in boron. (author)

A parameter study to determine the optimal source neutron energy in boron neutron capture therapy of brain tumours

Energy Technology Data Exchange (ETDEWEB)

Nievaart, V A [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Moss, R L [Joint Research Centre of the European Commission, Postbus 2, 1755ZG Petten (Netherlands); Kloosterman, J L [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Hagen, T H J J van der [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands); Dam, H van [Reactor Physics Department, Delft University of Technology, Mekelweg 15, 2629JB Delft (Netherlands)

2004-09-21

The values of the parameters used in boron neutron capture therapy (BNCT) to calculate a given dose to human tissue vary with patients due to different physical, biological and/or medical circumstances. Parameters include the tissue dimensions, the {sup 10}B concentration and the relative biological effectiveness (RBE) factors for the different dose components associated with BNCT. Because there is still no worldwide agreement on RBE values, more often than not, average values for these parameters are used. It turns out that the RBE-problem can be circumvented by taking into account all imaginable parameter values. Approaching this quest from another angle: the outcome will also provide the parameters (and values) which influence the optimal source neutron energy. For brain tumours it turns out that the {sup 10}B concentration, the RBE factors for {sup 10}B as well as fast neutrons, together with the dose limit set for healthy tissue, affect the optimal BNCT source neutron energy. By using source neutrons of a few keV together with neutrons of a few eV, it ensures that, under all imaginable circumstances, a maximum of alpha (and lithium) particles can be delivered in the tumour.

Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

Science.gov (United States)

Pasadhika, Sirichai; Rosenbaum, James T

2014-01-01

Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

MIDAS: a practical Bayesian design for platform trials with molecularly targeted agents.

Science.gov (United States)

Yuan, Ying; Guo, Beibei; Munsell, Mark; Lu, Karen; Jazaeri, Amir

2016-09-30

Recent success of immunotherapy and other targeted therapies in cancer treatment has led to an unprecedented surge in the number of novel therapeutic agents that need to be evaluated in clinical trials. Traditional phase II clinical trial designs were developed for evaluating one candidate treatment at a time and thus not efficient for this task. We propose a Bayesian phase II platform design, the multi-candidate iterative design with adaptive selection (MIDAS), which allows investigators to continuously screen a large number of candidate agents in an efficient and seamless fashion. MIDAS consists of one control arm, which contains a standard therapy as the control, and several experimental arms, which contain the experimental agents. Patients are adaptively randomized to the control and experimental agents based on their estimated efficacy. During the trial, we adaptively drop inefficacious or overly toxic agents and 'graduate' the promising agents from the trial to the next stage of development. Whenever an experimental agent graduates or is dropped, the corresponding arm opens immediately for testing the next available new agent. Simulation studies show that MIDAS substantially outperforms the conventional approach. The proposed design yields a significantly higher probability for identifying the promising agents and dropping the futile agents. In addition, MIDAS requires only one master protocol, which streamlines trial conduct and substantially decreases the overhead burden. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

Science.gov (United States)

Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

2011-01-01

The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

Monte Carlo codes use in neutron therapy

International Nuclear Information System (INIS)

Paquis, P.; Mokhtari, F.; Karamanoukian, D.; Pignol, J.P.; Cuendet, P.; Iborra, N.

1998-01-01

Monte Carlo calculation codes allow to study accurately all the parameters relevant to radiation effects, like the dose deposition or the type of microscopic interactions, through one by one particle transport simulation. These features are very useful for neutron irradiations, from device development up to dosimetry. This paper illustrates some applications of these codes in Neutron Capture Therapy and Neutron Capture Enhancement of fast neutrons irradiations. (authors)

[Antibiotic therapy of hospital-acquired pneumonia and its pharmacoeconomics].

Science.gov (United States)

Kolář, Milan; Htoutou Sedláková, Miroslava; Urbánek, Karel; Uvízl, Radomír; Adamus, Milan; Imwensi, O P

2016-03-01

Important hospital-acquired infections include pneumonia, mainly because of the increasing resistance of bacterial pathogens to antimicrobials and the associated potential failure of antibiotic therapy. The present study aimed at determining the most frequent etiological agents of hospital-acquired pneumonia (HAP) and assessing the relationship between 30-day mortality and adequacy of antibiotic therapy. Based on the obtained information, optimal patterns of antibiotic therapy were to be defined, including a pharmacoeconomic perspective. In patients with clinically confirmed HAP, bacterial etiological agents were identified, their susceptibility to antimicrobials was determined and statistical methods were used to assess the relationship between adequacy of antibiotic therapy and 30-day mortality. The study comprised 68 patients with clinically confirmed HAP. The most common etiological agents were strains of Pseudomonas aeruginosa (30.8 %), Klebsiella pneumoniae (23.1 %) and Burkholderia cepacia complex (15.4 %). Gram-negative bacteria accounted for 86.5 % of all bacterial pathogens. The overall mortality reached 42.5 %. In the subgroup of patients with inadequate antibiotic therapy, 30-day mortality was significantly higher (83.3 %) than in the subgroup with adequate therapy (30.0 %; p = 0.002). The risk for 30-day mortality was 2.78 times higher in case of inadequate antibiotic therapy (95%CI: 1.52-5.07). The proportion of Pseudomonas aeruginosa strains was significantly higher in the subgroup of patients with inadequate antibiotic therapy than in those with adequate therapy (67 % vs. 27 %; p = 0.032). Results of the present study suggest a significant relationship between mortality of patients with HAP and ineffective antibiotic therapy due to resistance of the bacterial pathogen. Thus, it is clear that initial antibiotic therapy must be based on qualified assumption of sufficient activity against the most common bacterial pathogens and results of surveillance

A stochastic multi-agent optimization model for energy infrastructure planning under uncertainty and competition.

Science.gov (United States)

2017-07-04

This paper presents a stochastic multi-agent optimization model that supports energy infrastruc- : ture planning under uncertainty. The interdependence between dierent decision entities in the : system is captured in an energy supply chain network, w...

Optional carbon capture

Energy Technology Data Exchange (ETDEWEB)

Alderson, T.; Scott, S.; Griffiths, J. [Jacobs Engineering, London (United Kingdom)

2007-07-01

In the case of IGCC power plants, carbon capture can be carried out before combustion. The carbon monoxide in the syngas is catalytically shifted to carbon dioxide and then captured in a standard gas absorption system. However, the insertion of a shift converter into an existing IGCC plant with no shift would mean a near total rebuild of the gasification waste heat recovery, gas treatment system and HRSG, with only the gasifier and gas turbine retaining most of their original features. To reduce the extent, cost and time taken for the revamping, the original plant could incorporate the shift, and the plant would then be operated without capture to advantage, and converted to capture mode of operation when commercially appropriate. This paper examines this concept of placing a shift converter into an IGCC plant before capture is required, and operating the same plant first without and then later with CO{sub 2} capture in a European context. The advantages and disadvantages of this 'capture ready' option are discussed. 6 refs., 2 figs., 4 tabs.

Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents.

Science.gov (United States)

Odenike, Olatoyosi

2017-12-08

In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS) has revolved around the azanucleosides, azacitidine and decitabine, which at lower doses are postulated to work predominantly via their effects on inhibition of DNA methyltransferases and consequent DNA hypomethylation. For patients who relapse after, or do not respond to, hypomethylating agent therapy, the outcome is dismal, and new agents and approaches that have the potential to alter the natural history of these diseases are desperately needed. Allogeneic stem cell transplant is the only known potentially curative approach in MDS, but its applicability has been limited by the advanced age of patients and attendant comorbidities. There is now an increasing array of new agents under clinical investigation in MDS that aim to exploit our expanding understanding of molecular pathways that are important in the pathogenesis of MDS. This review focuses on a critical appraisal of novel agents being evaluated in higher-risk MDS that go beyond the conventional hypomethylating agent therapies approved by the US Food and Drug Administration. © 2016 by The American Society of Hematology. All rights reserved.