External X-ray Irradiation Research Articles

Decomposition characteristics of a hypervalent iodine compound, 2-iodosobenzoic acid, exposed to monochromatic X-rays around the iodine L3-edge energy region

In clinical settings, the development of novel X-ray-activated caged compounds has been described as a key factor in both therapeutic and diagnostic applications to halt the action of specific medication, i.e., reactivation by external X-ray irradiation causing site-selective bond breakages, during delivery to target organs. In this work, we focused on a hypervalent iodine compound, namely 2-iodosobenzoic acid (IBA), as a candidate for the protecting group of X-ray-activated caged compounds, and investigated the decomposition reactions of IBA induced by X-ray irradiations around the iodine L3-edge energy region. Our results showed that X-irradiations induced bond breakages around the hypervalent iodine atom, and the associated decomposition rate was dependent on the irradiated X-ray photon energy. Particularly, X-ray absorption spectral changes and desorbed molecular fragments confirmed a significant molecular decomposition induced by one of the iodine L-shell excitations. Our findings suggest that the hypervalent iodine compound could be a very promising candidate for the design of novel X-ray-activated caged compounds.

Evaluation of the Applicability of External X-ray Radiation to Stimulate the Autoradiolysis Processes in Therapeutic Radiopharmaceuticals (Exemplified by [153Sm]Sm-PSMA-617 and [177Lu]Lu-PSMA-617)

The paper presents the results of a study on the radiolytic degradation of vector molecules in radiopharmaceuticals, caused by ionizing radiation from the radionuclide used in the preparations, in comparison with the equal dose of external X-ray irradiation. The dose factors for therapeutic radionuclides samarium-153 and lutetium-177 in aqueous solutions were estimated in geometry simulating the finished dosage form of radiopharmaceuticals (standard injection vial ) both by computational methods (in silico) and applying chemical dosimetry. Irradiation with external X-ray source to doses formed in volume of therapeutic radiopharmaceuticals with given radioactivity concentration was performed on an LNK-268 X-ray unit. Using the [153Sm]Sm-PSMA-617 and [177Lu]Lu-PSMA-617 radiopharmaceuticals as an instance, we compared the degree of radiolytic degradation and the profiles of radiolytic impurities formed as a result of both external X-ray irradiation and autoradiolysis. Qualitative coincidence of the impurity profiles formed in both cases was noted. It has been shown that external X-ray radiation can be used to simulate the autoradiolysis processes of radiopharmaceuticals if additional corrections are made for the type of radiation and dose rate.

Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma.

This study aimed to evaluate the radiosensitizing potential of Au@DTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM. Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose; 5×2 Gy or 2×5 Gy) combined with Au@DTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed. This work focused on the invading cancer cells after irradiation and their viability, aggressiveness, and recurrence potential were assessed using mitotic catastrophe quantification, MMP secretion analysis and neurosphere assays, respectively. In vitro clonogenic assays showed that Au@DTDTPA(Gd) nanoparticles exerted a radiosensitizing effect on U87 cells, and in vivo experiments suggested a benefit of the combined treatment "RT 2×5 Gy + Au@DTDTPA(Gd)" compared to RT alone. Invasion assays revealed that invasion distance tended to increase after irradiation alone, while the combined treatments were able to significantly reduce tumor invasion. Monitoring of U87-GFP tumor progression using organotypic cultures or intracerebral grafts confirmed the anti-invasive effect of Au@DTDTPA(Gd) on irradiated spheroids. Most importantly, the combination of Au@DTDTPA(Gd) with irradiation drastically reduced the number, the viability and the aggressiveness of tumor cells able to escape from U87 spheroids. Notably, the combined treatments significantly reduced the proportion of escaped cells with stem-like features that could cause recurrence. Combining Au@DTDTPA(Gd) nanoparticles and X-ray radiotherapy appears as an attractive therapeutic strategy to decrease number, viability and aggressiveness of tumor cells that escape and can invade the surrounding brain parenchyma. Hence, Au@DTDTPA(Gd)-enhanced radiotherapy opens up interesting perspectives for glioblastoma treatment.

Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells.

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g., in combination with radiotherapy or endoradiotherapy, represents an interesting treatment option. Based on our own findings that nitric oxide (NO)-releasing and celecoxib-derived COX-2 inhibitors (COXIBs) showed promising radiosensitizing effects in vitro, we herein present the development of a series of eight novel NO-COXIBs differing in the peripheral substitution pattern and their chemical and in vitro characterization. COX-1 and COX-2 inhibition potency was found to be comparable to the lead NO-COXIBs, and NO-releasing properties were demonstrated to be mainly influenced by the substituent in 4-position of the pyrazole (Cl vs. H). Introduction of the N-propionamide at the sulfamoyl residue as a potential prodrug strategy lowered lipophilicity markedly and abolished COX inhibition while NO-releasing properties were not markedly influenced. NO-COXIBs were tested in vitro for a combination with single-dose external X-ray irradiation as well as [177Lu]LuCl3 treatment in HIF2α-positive mouse pheochromocytoma (MPC-HIF2a) tumor spheroids. When applied directly before X-ray irradiation or 177Lu treatment, NO-COXIBs showed radioprotective effects, as did celecoxib, which was used as a control. Radiosensitizing effects were observed when applied shortly after X-ray irradiation. Overall, the NO-COXIBs were found to be more radioprotective compared with celecoxib, which does not warrant further preclinical studies with the NO-COXIBs for the treatment of pheochromocytoma. However, evaluation as radioprotective agents for healthy tissues could be considered for the NO-COXIBs developed here, especially when used directly before irradiation.

X-ray-facilitated redox cycling of nanozyme possessing peroxidase-mimicking activity for reactive oxygen species-enhanced cancer therapy

Nanomaterials with shifting or mixed redox states is one of the most common studied nanozyme with peroxidase-like activity for chemodynamic therapy (CDT), which can decompose hydrogen peroxide (H2O2) of tumor microenvironment into highly toxic reactive oxygen species (ROS) by a nano-catalytic way. However, most of them exhibit an insufficient catalytic efficiency due to their dependence on catalytic condition. Herein, a potential methodology is proposed to enhance their enzymatic activity by accelerating the redox cycling of these nanomaterials with shifting or mixed redox states in the presence of X-ray. In this study, the nanocomposite consisting of SnS2 nanoplates and Fe3O4 quantum dots with shifting or mixed redox states (Fe2+/Fe3+) is used to explore the strategy. Under external X-ray irradiation, SnS2 cofactor as electron donor can be triggered to transfer electrons to Fe3O4, which promotes the regeneration of Fe2+ sites on the surface of the Fe3O4. Consequently, the regenerated Fe2+ sites react with the overexpressed H2O2 to persistently generate ROS for enhanced tumor therapy. The designed nanocomposite displays the synergistic effects of radiotherapy and CDT. The strategy provides a new avenue for the development of artificial nanozymes with shifting or mixed redox states in precise cancer treatments based on X-ray-enhanced enzymatic efficacy.

Development of Fe3O4 core\u2013TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization

BackgroundNeuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro.ResultsThe uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs.ConclusionsThe intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization – use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides.Graphic abstract

HIF2alpha-Associated Pseudohypoxia Promotes Radioresistance in Pheochromocytoma: Insights from 3D Models

Simple SummaryLow oxygen levels (hypoxia) as well as genetic defects activating hypoxia signaling pathways (pseudohypoxia) are known to contribute to tumorigenesis and therapy resistance in various cancers. The genetic background of pheochromocytomas and paragangliomas is well characterized and indicates that pseudohypoxia plays a role in tumor formation and metastatic spread in a subgroup of these tumors. It is, however, unknown how pseudohypoxia affects susceptibility to radiation treatments, which is of particular interest, since targeted radionuclide therapy is one of the few options used against metastatic pheochromocytomas and paragangliomas. To date, no curative treatment is available for metastatic disease. Here, we report on the radioprotective effects of pseudohypoxia against both external irradiation and beta particle-emitting lutetium-177 in a pheochromocytoma tumor spheroid model expressing hypoxia-inducible factor 2 alpha. Our findings highlight hypoxia signaling pathways as potential targets for neo-adjuvant—in particular, radiosensitizing—therapies in pseudohypoxic pheochromocytomas and paragangliomas.Pheochromocytomas and paragangliomas (PCCs/PGLs) are rare neuroendocrine tumors arising from chromaffin tissue located in the adrenal or ganglia of the sympathetic or parasympathetic nervous system. The treatment of non-resectable or metastatic PCCs/PGLs is still limited to palliative measures, including somatostatin type 2 receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE as one of the most effective approaches to date. Nevertheless, the metabolic and molecular determinants of radiation response in PCCs/PGLs have not yet been characterized. This study investigates the effects of hypoxia-inducible factor 2 alpha (HIF2α) on the susceptibility of PCCs/PGLs to radiation treatments using spheroids grown from genetically engineered mouse pheochromocytoma (MPC) cells. The expression of Hif2α was associated with the significantly increased resistance of MPC spheroids to external X-ray irradiation and exposure to beta particle-emitting [177Lu]LuCl3 compared to Hif2α-deficient controls. Exposure to [177Lu]LuCl3 provided an increased long-term control of MPC spheroids compared to single-dose external X-ray irradiation. This study provides the first experimental evidence that HIF2α-associated pseudohypoxia contributes to a radioresistant phenotype of PCCs/PGLs. Furthermore, the external irradiation and [177Lu]LuCl3 exposure of MPC spheroids provide surrogate models for radiation treatments to further investigate the metabolic and molecular determinants of radiation responses in PCCs/PGLs and evaluate the effects of neo-adjuvant—in particular, radiosensitizing—treatments in combination with targeted radionuclide therapies.

αvβ3-Specific Gold Nanoparticles for Fluorescence Imaging of Tumor Angiogenesis.

This paper reports on the development of tumor-specific gold nanoparticles (AuNPs) as theranostic tools intended for target accumulation and the detection of tumor angiogenesis via optical imaging (OI) before therapy is performed, being initiated via an external X-ray irradiation source. The AuNPs were decorated with a near-infrared dye, and RGD peptides as the tumor targeting vector for αvβ3-integrin, which is overexpressed in tissue with high tumor angiogenesis. The AuNPs were evaluated in an optical imaging setting in vitro and in vivo exhibiting favorable diagnostic properties with regards to tumor cell accumulation, biodistribution, and clearance. Furthermore, the therapeutic properties of the AuNPs were evaluated in vitro on pUC19 DNA and on A431 cells concerning acute and long-term toxicity, indicating that these AuNPs could be useful as radiosensitizers in therapeutic concepts in the future.

Co-exposure to internal and external radiation alters cesium biokinetics and retention in mice

Exposures in post-accidental situations are complex and include both external exposure and internal contamination with several radionuclides. However, in vivo and in vitro studies generally use simplified exposures, while a recent study suggested that combined external irradiation and internal contamination may induce more severe biological effects compared to single exposures. In an attempt to test the hypothesis of potential non-additive effects of multiple radiological exposures, we used a mouse model of combined external x-ray irradiation at 1 and 5 Gy and internal contamination with injection of 20 KBq 137Cs. The results showed differential kinetics of 137Cs elimination in irradiated animals compared to sham-irradiated, 137Cs injected animals. Moreover, changes in plasma potassium and in relative testis weight were observed 38 days after irradiation and injection in co-exposed animals compared to 137Cs injection alone. These results demonstrate that an external exposure combined with an internal contamination may lead to unexpected changes in biokinetics of radionuclides and biological effects compared to single exposures.

Наночастицы сложного оксида железа, нагруженные цисплатином: цитостатические свойства при комбинации с рентгеновским излучением

Описана методика получения устойчивого конъюгата наночастиц оксида железа и цисплатина, определено оптимальное соотношение концентраций наночастиц и цисплатина. Проведен сравнительный анализ цитотоксического действия наночастиц, нагруженных цисплатином, и чистого цисплатина, без и при внешнем рентгеновском облучении клеток линии HeLa. Показано, что рентгеновское облучение клеток линии HeLa усиливает цитотоксическое действие конъюгата наночастицы с цисплатином на 35 % при p < 0,05, но не цисплатина в свободной форме.

X-ray irradiation of the winds in binaries with massive components

Binaries with hot massive components are strong X-ray sources. Besides the intrinsic X-ray emission of individual binary members originating in their winds, X-ray emission stems from the accretion on the compact companion or from wind collision. Since hot star winds are driven by the light absorption in the lines of heavier elements, wind acceleration is sensitive to the ionization state. Therefore, the over-ionization induced by external X-ray source strongly influences the winds of individual components. We studied the effect of external X-ray irradiation on hot star winds. We used our kinetic equilibrium (NLTE) wind models to estimate the influence of external X-ray ionization for different X-ray luminosities and source distances. The models are calculated for parameters typical of O stars. The influence of X-rays is given by the X-ray luminosity, by the optical depth between a given point and the X-ray source, and by a distance to the X-ray source. Therefore, the results can be interpreted in the diagrams of X-ray luminosity vs.~the optical depth parameter. X-rays are negligible in binaries with low X-ray luminosities or at large distances from the X-ray source. The influence of X-rays is stronger for higher X-ray luminosities and in closer proximity of the X-ray source. There is a forbidden area with high X-ray luminosities and low optical depth parameters, where the X-ray ionization leads to wind inhibition. There is excellent agreement between the positions of observed stars in these diagrams and our predictions. All wind-powered high-mass X-ray binary (HMXB) primaries lie outside the forbidden area. Many of them lie close to the border of the forbidden area, indicating that their X-ray luminosities are self-regulated. We discuss the implications of our work for other binary types.

Multifunctional Bi2S3/PLGA nanocapsule for combined HIFU/radiation therapy

A multifunctional organic-inorganic hybrid nanocapsule based on Bi2S3-embedded poly (lactic-co-glycolic acid) (PLGA) nanocapsule has been elaborately designed to combine the merits of both polymeric shell structure and Bi2S3 nanoparticles. Hydrophobic Bi2S3 nanoparticles were successfully introduced into the PLGA nanocapsules via a facile and efficient water/oil/water (W/O/W) emulsion strategy. The elastic polymeric PLGA shell provides the excellent capability of ultrasound contrast imaging to the Bi2S3/PLGA. Meanwhile, the potential of these microcapsules to enhance the high intensity focused ultrasound (HIFU) therapy was demonstrated. Importantly, this research provided the first example of both in vitro and in vivo to demonstrate the radiosensitization effect of Bi2S3-embedded PLGA hybrid nanocapsules against prostate cancer under external X-ray irradiation. Thus, the successful integration of the Bi2S3 and PLGA nanocapsules provided an alternative strategy for the highly efficient ultrasound guided HIFU/RT synergistic therapy.

Phase II clinical study of boron neutron capture therapy combined with X-ray radiotherapy/temozolomide in patients with newly diagnosed glioblastoma multiforme—Study design and current status report

Recently, we reported our clinical experiences of boron neutron capture therapy (BNCT) for the newly diagnosed glioblastoma. The major differences of our protocol from the other past studies were simultaneous use of both sodium borocapate and boronophenylalanine, and combination with fractionated X-ray irradiation. These results showed the efficacy of combination therapy with external beam X-ray irradiation and BNCT. For our future study, we planned the multi-centric phase II clinical study for newly diagnosed glioblastoma patients in Japan (OSAKA-TRIBRAIN0902, NCT00974987).

Combining Sirolimus-eluting Stents and External Irradiation in Cholesterol-fed Rabbits Increased Incomplete Stent Apposition and Decreased Re-endothelialization

Restenosis after the implantation of a drug-eluting stent or after vascular irradiation therapy shares similar physiopathological mechanisms. No experimental data are currently available on vascular wall behavior after external irradiation on arteries stented with sirolimus-eluting stents (SES). Ten New Zealand white rabbits received a 0.5% cholesterol-enriched chow for 1 month. Bilateral iliac artery stent implantation was then performed with an SES (Cypher; Cordis Corp). The animals were randomized into either an irradiated group (I, 2 Gy external x-ray irradiation, n = 5) or a control group (C, n = 5). The cholesterol-enriched chow was continued for 1 additional month after stent implantation. The stented arteries were harvested for histological analyses. The number and the percentage of incompletely apposed stents struts (IASS) were significantly higher in irradiated versus control group (3.05 +/- 0.46 vs. 1.57 +/- 0.27 IASS, P < 0.01, and 28.44% +/- 3.97% vs. 15.2% +/- 2.46% of IASS, P < 0.01, respectively). The mean neointimal thickness behind the IASS was also higher in the irradiated group (I: 28.3 +/- 2.5 microm vs. C: 18.2 +/- 2.3 microm, P < 0.01). Re-endothelialization was lower in irradiated group (I: 44.6% +/- 17.5% vs. C: 75.2% +/- 5.7%, P < 0.01). The present study revealed that low-dose external irradiation increased incomplete stent apposition and reduced re-endothelialization of SES. These results underscore the potential deleterious cumulative side effects of these 2 procedures to prevent restenosis.

Survival benefit from boron neutron capture therapy for the newly diagnosed glioblastoma patients

Objective: Since 2002–2007, we applied boron neutron capture therapy (BNCT) to >50 cases of malignant gliomas (MGs) with epithermal neutron irradiations. Recently, we showed the early radiographical improvement of malignant glioma patients by our modified BNCT, with simultaneous use of BPA (borono-phenylalanine) and BSH (sodium borocaptate). In this time, we focused on the survival benefit from BNCT for the newly diagnosed glioblastoma patients. Methods: BNCT group including 21 newly histological confirmed glioblastoma patients treated with surgical removal followed by BNCT in Osaka Medical College during 2002–2006 period. Ten patients were treated with BNCT only, and in the other 11 patients, 20–30 Gy fractionated external beam X-ray irradiation therapy (XRT) was performed after BNCT. No chemotherapy was administered until tumor progression was observed. Results: Treatments were well tolerated. Any kind of acute systemic or local severe toxicity were not demonstrated. Mean over all survival of the patients treated by BNCT was 20.7 and the median was 15.6 months with 2-years survival of 25%. Stratification by RPA criteria showed 6, 6, 8 and 1 patients, respectively, in classes III–VI. Three patients out of six in class III and one out of eight in class V are alive at the end point of this study. All the patients in classes IV and VI died. Median survival time for the BNCT group compared to the RTOG database was as follows: 20.6 months vs. 17.9 months for class III; 16.9 months vs. 11.1 months for class IV; 13.2 months vs. 8.9 months for class V. Conclusion: The RTOG RPA prognostic criteria were helpful in establishing which class of glioma patients could potentially benefit from BNCT. BNCT showed a survival benefit in all of the RPA classes of the RTOG database not only for the good prognosis group.

The effect of ionizing irradiation on vasomotor reactivity in the rat thoracic aorta in vitro

Purpose: Ionizing irradiation inhibits restenosis in animal models and human. Vasomotor tone preservation during and after radiation therapy is of clinical importance. We therefore investigated vascular reactivity following radiation therapy. Methods and Materials: Wistar Sabra rats were treated with a single dose of 1000 cGy external X-ray irradiation. Vascular reactivity of 192 segments of rat thoracic aorta was studied in vitro in four groups (12 rats in each group, four segments from each aorta). Immediately after in vivo irradiation, immediately after ex vivo irradiation, 1 month after irradiation, and no irradiation (control). Results: Vasoconstriction to phenylephrine (PE) 10 −9–10 −5 M or KCl 118.0 mM in all the irradiated groups was similar to controls. Endothelium-dependent vasorelaxation to acetylcholine (ACh) 10 −9–10 −5 M in segments studied immediately after in vivo irradiation was increased compared to controls at all concentrations (109.7±35. and 90.0±40.0%, respectively, at 10 −5 M, P=.006). Endothelium-independent relaxation to nitroglycerin 10 −9–10 −5 M in all irradiated groups was similar to controls. Conclusions: External-ionizing irradiation with 1000 cGy in the rat aortic model induces acute and transient increase in endothelium-dependent relaxation to ACh, and does not alter vasoconstriction and endothelium-independent relaxation.

Enhancement of Thermal Smoothing Effect on Laser Imprint with Soft X-Ray Radiation

The initial imprint of mass perturbation due to spatial nonuniformity of laser intensity is one of the most important issues in laser fusion research. Several imprint mitigation schemes by the use of soft X-ray radiation have been proposed to enhance the thermal smoothing effect within the conduction region. One of the schemes uses external X-ray irradiation prior to laser incidence to produce preformed plasma. Another has a low-density foam layer and high-Z material to heat the foam radiatively and make it uniform in density.

The treatment results of 40 patients with localized endobronchial cancer with external beam irradiation and intraluminal irradiation using low dose rate 192Ir thin wires with a new catheter

Background and purpose: While bronchial intraluminal irradiation is valued highly as a useful palliative treatment for lung cancer, its role as a curative treatment is unclear. The treatment results of 40 localized enbobronchial tumors (including tracheal cancer) who underwent external beam irradiation (EBR) and intraluminal irradiation (IR) as a curative treatment is reported, and the role of combined EBR and IR as a curative potential treatment is examined. Materials and methods: Forty patients, including 22 with roentgenographically occult lung cancer (ROLC), 14 (18 lesions) with postoperative recurrent lung cancer (PORLC) and four with tracheal cancer, who underwent EBR and IR from February 1987 to August 1996, were studied. IR was conducted using low dose rate (1.48 GBq) 192Ir thin wires at a bronchial mucosal dose of 4–6 Gy per fraction, with a total dose of 10–57 Gy (median 28 Gy). All patients were also given combined external Linac X-ray irradiation for a total dose of 30–77 Gy (median 52 Gy). Results: As for the primary effect, complete response (CR) was obtained in all 22 ROLC cases; CR was obtained in 12 (16 lesions), partial response (PR) in one and minor response (MR) in one of the PORLC cases; and CR was obtained in three and PR in one of the tracheal cancer cases. The 3-year and 5-year local control rate by Kaplan–Meier method was 75 and 65%, respectively. Twenty-two patients survived for 3 years or longer. Complications included one case each of fatal tracheal hemorrhage, bronchial mucosal ulcer and bronchial stenosis. Conclusions: Combined EBR and IR is useful as a curative potential treatment, and long-term survival can be expected in ROLC, tracheal cancer and a portion of PORLC cases.

External beam irradiation inhibits neointima hyperplasia after injury-induced arterial smooth muscle cell proliferation

Purpose: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examines the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. Methods and Materials: Thirty male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 1200 cGy (n = 10), 1600 cGy (n = 10), or 2000 cGy (n = 10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after 21 days and the central arteries of both ears were fixed for morphometric measurements. Results: Mean (±SD) neointimal area was 0.062 ± 0.005 mm 2 (1200 cGy), 0.022 ± 0.005 mm 2 (1600 cGy), and 0.028 ± 0.006 mm 2 in irradiated arteries compared with 0.081 ± 0,009 mm 2 in the control group. Mean (±SD) luminal area was 0.049 ± 0.004 mm 2 (1200 cGy), 0.059 ± 0.002 mm 2 (1600 cGy), and 0.072 ± 0.006 mm 2 (2000 cGy) in irradiated arteries compared with 0.043 ± 0.008 mm 2 in the control group. The differences in neointimal and luminal area between control and irradiated arteries were significant ( p < 0.05) for the 1600 and 2000 cGy group only. Conclusion: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. Marked reductions in neointimal proliferation were demonstrated in vessels subject to 1600 and 2000 cGy radiation; a less prominent effect was noted for 1200 cGy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.

Magnetoplastic effect in nonmagnetic crystals

The main features of the magnetoplastic effect displaying itself in dislocation displacements in nonmagnetic crystals under the action of external magnetic field are briefly discussed. The influences of external electric field and X-ray irradiation on the magnetoplastic effect are demonstrated for NaCl and LiF crystals. A magnetic induction threshold B c below which the magnetoplastic effect does not exist is predicted and experimentally observed in Al, NaCl and LiF crystals. The existence of a threshold is associated with the fact that for B < B c the spin-lattice relaxation time τ slc in a system is less than the time required for a spin evolution in a magnetic field resulting in the removal of the spin forbiddenness of a process that ‘switches off’ the dislocation-pinning-center interaction. It is shown that the threshold field B c is sensitive to temperature and X-ray irradiation of the samples.