Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restr...Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repai展开更多
Objective:Cancer cell radioresistance is a stumbling block in radiation therapy.The activity in the nuclear factor kappa B(NFκB)pathway correlates with anti-apoptotic mechanisms and increased radioresistance.The IKK ...Objective:Cancer cell radioresistance is a stumbling block in radiation therapy.The activity in the nuclear factor kappa B(NFκB)pathway correlates with anti-apoptotic mechanisms and increased radioresistance.The IKK complex plays a major role in NFκB activation upon numerous signals.In this study,we examined the interaction between ionizing radiation(IR)and different members of the IKK-NFκB pathway,as well as upstream activators,RAF1,ERK,and AKT1.Methods:The effect of 4 Gy of IR on the expression of the RAF1-ERK-IKK-NFκB pathway was examined in A549 and H1299 lung cancer cell lines using Western blot analysis and confocal microscopy.We examined changes in radiation sensitivity using gene silencing or pharmacological inhibitors of ERK and IKKβ.Results:IKKα,IKKγ,and IκBαincreased upon exposure to IR,thereby affecting nuclear levels of NFκB(phospho-p65).ERK inhibition or si RNA-mediated down-regulation of RAF1 suppressed the post-irradiation survival of the examined lung cancer cell lines.A similar effect was detected on survival upon silencing IKKα/IKKγor inhibiting IKKβ.Conclusions:Exposure of lung cancer cells to IR results in NFκB activation via IKK.The genetic or pharmacological blockage of the RAF1-ERK-IKK-NFκB pathway sensitizes cells to therapeutic doses of radiation.Therefore,the IKK pathway is a promising target for therapeutic intervention in combination with radiotherapy.展开更多
Understanding the effects of ionising radiation (IR) on plants has been a major focus of research. Acute high-dose effects are well-documented and understood (mainly through laboratory testing). Lower doses, on the ot...Understanding the effects of ionising radiation (IR) on plants has been a major focus of research. Acute high-dose effects are well-documented and understood (mainly through laboratory testing). Lower doses, on the other hand, are less understood, as low dosage research is controversial, and there are only a few studies that use low and ecologically relevant IR levels, particularly those conducted under controlled conditions. The effect of low gamma radiation was investigated in this study using Vicia faba L., Vigna radiata L., and Pisum sativum L. Healthy and viable seeds of these plants were irradiated with varying doses of gamma radiation (Cs<sup>−</sup><sup>137</sup> source) and sown under controlled environmental conditions. The doses/dose rates used were within the scope of the International Commission on Radiological Protection’s Derived Consideration Reference Level (DCRL) for these groups of plants (1 - 10 mGy∙d<sup>−1</sup>), so this study tested this DCRL. Observations were made on certain germination parameters and growth traits like germination percentage and rate, shoot and root length, seed weight, number of leaves, wet and dry biomass, plant height, leaf chlorophyll content, and leaf area. In the germination phase, the doses employed in this experiment did not affect the seeds’ weight, germination percentage, and rate, but there were some interesting effects on the root and shoot length;as all irradiated groups performed better than the control group (particularly the 16.2 mGy and 48.5 mGy dose in V. radiata and P. sativum, while the 1070 mGy dose had the highest value in V. faba). However, the plants were able to compensate for the effects observed in the germination phase and by the end of the experiment, there were no statistically significant effects (at 0.05 p level) in all the morphometric parameters studied;the visible organs appeared normal, and growth rate was normal. This study, therefore, concludes that the DCRL used to protect these groups of plants from the effec展开更多
Cystic fibrosis(CF)is the most common autosomal recessive disease of the Caucasian population worldwide,with respiratory disease remaining the most relevant source of morbidity and mortality.Computed tomography(CT)is ...Cystic fibrosis(CF)is the most common autosomal recessive disease of the Caucasian population worldwide,with respiratory disease remaining the most relevant source of morbidity and mortality.Computed tomography(CT)is frequently used for monitoring disease complications and progression.Over the last fifteen years there has been a six-fold increase in the use of CT,which has lead to a growing concern in relation to cumulative radiation exposure.The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality,but fulfil the requirements of a diagnostic quality CT.Dose-optimisation,particularly in CT,is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 m Sv,a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation.This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.展开更多
Background: The radiosensitizing effect of Photofrin II has been demonstrated in vitro and in animal models, even in tumor models known to be highly radioresistant, such as glioblastoma and bladder carcinoma. Radio-ad...Background: The radiosensitizing effect of Photofrin II has been demonstrated in vitro and in animal models, even in tumor models known to be highly radioresistant, such as glioblastoma and bladder carcinoma. Radio-adaptive doses are also known to lead to an augmented cell or tissue reaction. The aim of this study was to investigate potential synergistic or additive effects when combining the two methods in vitro for an improved therapeutic concept in bladder cancer. Material and Methods: RT4 human bladder carcinoma cell line and HCV29 human bladder epithelium cells were seeded and incubated with various concentrations of Photofrin II. The cells were additionally irradiated with ionizing radiation (0.05 Gy/2 Gy/0.05 Gy + 2 Gy). Cells without Photofrin II incubation and irradiation served as controls. The cell survival was evaluated. Results: The survival rate of both cell lines, RT4 and HCV29, did not differ significantly when incubated with a non-toxic concentration of Photofrin II and exposed to a pre-irradiation dose of 0.05 Gy prior to the 2 Gy radiation fraction, compared to cells exposed to Photofrin II plus a 2 Gy ionizing radiation. Conclusion: The combination of both methods did neither demonstrate a synergistic or additive effect nor did it lead to a negative influence of both modulating factors in an in vitro setting.展开更多
Incidences of head and neck squamous cell carcinoma(HNSCC)have been on the rise in the last few decades,with a significant risk factor being human papillomavirus(HPV)type-16/18 infection,particularly in the developmen...Incidences of head and neck squamous cell carcinoma(HNSCC)have been on the rise in the last few decades,with a significant risk factor being human papillomavirus(HPV)type-16/18 infection,particularly in the development of oropharyngeal cancers.Radiotherapy(RT)is an important treatment modality for HNSCC,where it promotes extensive cellular DNA damage leading to the therapeutic effect.It has been well-established that HPV-positive HNSCC display better response rates and improved survival following RT compared to HPV-negative HNSCC.The differential radiosensitivity has been largely associated with altered cellular DNA damage response mechanisms in HPV-positive HNSCC,and particularly with the signaling and repair of DNA double strand breaks.However,other factors,particularly hypoxia present within the solid cancer,have a major impact on relative radioresistance.Consequently,recent approaches aimed at enhancing the radiosensitivity of HNSCC have largely centered on targeting key proteins involved in DNA repair,DNA damage checkpoint activation,and hypoxia signaling.These studies have utilised in vitro and in vivo models of HPV-positive and HPV-negative HNSCC and examined the impact of specific inhibitors against the targets in combination with radiation in suppressing HNSCC cell growth and survival.Here,accumulating evidence has shown that targeting enzymes including poly(ADP-ribose)polymerase,ataxia telangiectasia and Rad-3 related,DNA-dependent protein kinase catalytic subunit,and checkpoint kinase 1 can radiosensitise HNSCC cells which should be taken forward in further preclinical studies,with the goal of optimizing the future effective RT treatment of HNSCC.展开更多
In this work,the results of an experimental study of the impulse characteristic of practical ground electrodes consisting of horizontal conductors of various lengths and full-scale tower footings were reported.These e...In this work,the results of an experimental study of the impulse characteristic of practical ground electrodes consisting of horizontal conductors of various lengths and full-scale tower footings were reported.These electrodes were installed at an outdoor test site having nonuniform soil,with equipment facilities for generating low-and high-magnitude impulse currents.The tests on the horizontal electrode were used to determine the effective length,the voltage and current distribution along the electrode length and the effect of the injection point along the electrode.The tests on the tower footings were used to determine impulse resistance and demonstrate its non-linear variation with current magnitude.Computer simulations of the test electrodes using the electromagnetic field method showed good agreement with the measured result.展开更多
The combination of CrO4^2-anion and N,N′-dimethylformamide(DMF)-containing solvent helps to stabilize an atom-precise ultrasmall Ag6 kernel into a 52-nuclei silver shell,giving a core-shell Ag6@Ag52 wheel-like struct...The combination of CrO4^2-anion and N,N′-dimethylformamide(DMF)-containing solvent helps to stabilize an atom-precise ultrasmall Ag6 kernel into a 52-nuclei silver shell,giving a core-shell Ag6@Ag52 wheel-like structure(SD/Ag58b).The solution behavior and photocurrent response property were investigated in details.展开更多
In the present study the first 20 microatoms of the periodic table are named as bioatoms, since they are needed for biochemical functions and services to life itself. The rationale behind this project is the detailed ...In the present study the first 20 microatoms of the periodic table are named as bioatoms, since they are needed for biochemical functions and services to life itself. The rationale behind this project is the detailed analysis of the ionization energy of the electrons in the inside of the bioatoms and their orderly arrangement at specific positions. Such position of the electrons is harmonized with the succession of their energy values in their logarithmic curves. The compelling arrangement of each electron at a particular place would not be feasible in the absence of an energy offset, which is a proton. The latter would hold electrons on their proper position. These fundamental aspects of our project receive such strong support from the quantum theory, according to which it is the electromagnetic interaction between electrons and protons by the exchange of photons, which hold them together in the atoms. According to our proposed model, the protons of the aforementioned proton—electron twins, are distributed on distinct positions which are the junctions of a primary network, coupled with their electrons, in a secondary network. The geometry and distance of the protons, in the plexus, is constant and is calculated at 8, 42 ?. This was estimated by a mathematical analysis of the proposed model, as discussed further. Our study has shown that electrons in the specific positions are moving in a symmetrical oscillation in the length of a channel, in vacuum, under the Coulomb forces. Moreover, the chemical evidence suggests that electrons, in an atom, have their own separate orbit, and that these orbits are closely interrelated.展开更多
基金supported by grant of the Science and Technology Planning Project of Guangdong Province (2010B060900052 and 2009B030801186)the Fundamental Research Funds for the Central Universities (the Young Teacher Training Project of Sun Yat-sen University 09ykpy12)the Medical Scientific Research Project of Zhuhai City (2012003)
文摘Radiation is an important modality in cancer treatment, and eighty percent of cancer patients need radiotherapy at some point during their clinical management. However, radiation-induced damage to normal tissues restricts the therapeutic doses of radiation that can be delivered to tumours and thereby limits the effectiveness of the treatment. The use of radioprotectors represents an obvious strategy to obtain better tumour control using a higher dose in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical efficacy owing to their inherent toxicity and high cost. Hence, the development of radioprotective agents with lower toxicity and an extended window of protection has attracted a great deal of attention, and the identification of alternative agents that are less toxic and highly effective is an absolute necessity. Recent studies have shown that alpha-2-macroglobulin（α2M） possesses radioprotective effects. α2M is a tetrameric, disulfide-rich plasma glycoprotein that functions as a nonselective inhibitor of different types of non-specific proteases and as a carrier of cytokines, growth factors, and hormones. α2M induces protein factors whose interplay underlies radioprotection, which supports the idea that α2M is the central effector of natural radioprotection in the rat. Pretreatment with α2M has also induced a significant reduction of irradiation-induced DNA damage and the complete restoration of liver and body weight. Mihailovi？ et al. concluded that the radioprotection provided by α2M was in part mediated through cytoprotection of new blood cells produced in the bone marrow; these authors also indicated that an important aspect of the radioprotective effect of amifostine was the result of the induction of the endogenous cytoprotective capability of α2M. The radioprotective effects of α2M are possibly due to antioxidant, antifibrosis, and anti-inflammatory functions, as well as the maintenance of homeostasis, and enhancement of the DNA repai
文摘Objective:Cancer cell radioresistance is a stumbling block in radiation therapy.The activity in the nuclear factor kappa B(NFκB)pathway correlates with anti-apoptotic mechanisms and increased radioresistance.The IKK complex plays a major role in NFκB activation upon numerous signals.In this study,we examined the interaction between ionizing radiation(IR)and different members of the IKK-NFκB pathway,as well as upstream activators,RAF1,ERK,and AKT1.Methods:The effect of 4 Gy of IR on the expression of the RAF1-ERK-IKK-NFκB pathway was examined in A549 and H1299 lung cancer cell lines using Western blot analysis and confocal microscopy.We examined changes in radiation sensitivity using gene silencing or pharmacological inhibitors of ERK and IKKβ.Results:IKKα,IKKγ,and IκBαincreased upon exposure to IR,thereby affecting nuclear levels of NFκB(phospho-p65).ERK inhibition or si RNA-mediated down-regulation of RAF1 suppressed the post-irradiation survival of the examined lung cancer cell lines.A similar effect was detected on survival upon silencing IKKα/IKKγor inhibiting IKKβ.Conclusions:Exposure of lung cancer cells to IR results in NFκB activation via IKK.The genetic or pharmacological blockage of the RAF1-ERK-IKK-NFκB pathway sensitizes cells to therapeutic doses of radiation.Therefore,the IKK pathway is a promising target for therapeutic intervention in combination with radiotherapy.
文摘Understanding the effects of ionising radiation (IR) on plants has been a major focus of research. Acute high-dose effects are well-documented and understood (mainly through laboratory testing). Lower doses, on the other hand, are less understood, as low dosage research is controversial, and there are only a few studies that use low and ecologically relevant IR levels, particularly those conducted under controlled conditions. The effect of low gamma radiation was investigated in this study using Vicia faba L., Vigna radiata L., and Pisum sativum L. Healthy and viable seeds of these plants were irradiated with varying doses of gamma radiation (Cs<sup>−</sup><sup>137</sup> source) and sown under controlled environmental conditions. The doses/dose rates used were within the scope of the International Commission on Radiological Protection’s Derived Consideration Reference Level (DCRL) for these groups of plants (1 - 10 mGy∙d<sup>−1</sup>), so this study tested this DCRL. Observations were made on certain germination parameters and growth traits like germination percentage and rate, shoot and root length, seed weight, number of leaves, wet and dry biomass, plant height, leaf chlorophyll content, and leaf area. In the germination phase, the doses employed in this experiment did not affect the seeds’ weight, germination percentage, and rate, but there were some interesting effects on the root and shoot length;as all irradiated groups performed better than the control group (particularly the 16.2 mGy and 48.5 mGy dose in V. radiata and P. sativum, while the 1070 mGy dose had the highest value in V. faba). However, the plants were able to compensate for the effects observed in the germination phase and by the end of the experiment, there were no statistically significant effects (at 0.05 p level) in all the morphometric parameters studied;the visible organs appeared normal, and growth rate was normal. This study, therefore, concludes that the DCRL used to protect these groups of plants from the effec
文摘Cystic fibrosis(CF)is the most common autosomal recessive disease of the Caucasian population worldwide,with respiratory disease remaining the most relevant source of morbidity and mortality.Computed tomography(CT)is frequently used for monitoring disease complications and progression.Over the last fifteen years there has been a six-fold increase in the use of CT,which has lead to a growing concern in relation to cumulative radiation exposure.The challenge to the medical profession is to identify dose reduction strategies that meet acceptable image quality,but fulfil the requirements of a diagnostic quality CT.Dose-optimisation,particularly in CT,is essential as it reduces the chances of patients receiving cumulative radiation doses in excess of 100 m Sv,a dose deemed significant by the United Nations Scientific Committee on the Effects of Atomic Radiation.This review article explores the current trends in imaging in CF with particular emphasis on new developments in dose optimisation.
文摘Background: The radiosensitizing effect of Photofrin II has been demonstrated in vitro and in animal models, even in tumor models known to be highly radioresistant, such as glioblastoma and bladder carcinoma. Radio-adaptive doses are also known to lead to an augmented cell or tissue reaction. The aim of this study was to investigate potential synergistic or additive effects when combining the two methods in vitro for an improved therapeutic concept in bladder cancer. Material and Methods: RT4 human bladder carcinoma cell line and HCV29 human bladder epithelium cells were seeded and incubated with various concentrations of Photofrin II. The cells were additionally irradiated with ionizing radiation (0.05 Gy/2 Gy/0.05 Gy + 2 Gy). Cells without Photofrin II incubation and irradiation served as controls. The cell survival was evaluated. Results: The survival rate of both cell lines, RT4 and HCV29, did not differ significantly when incubated with a non-toxic concentration of Photofrin II and exposed to a pre-irradiation dose of 0.05 Gy prior to the 2 Gy radiation fraction, compared to cells exposed to Photofrin II plus a 2 Gy ionizing radiation. Conclusion: The combination of both methods did neither demonstrate a synergistic or additive effect nor did it lead to a negative influence of both modulating factors in an in vitro setting.
基金Fabbrizi MR and Parsons JL are supported by North West Cancer Research(No.CR1197).
文摘Incidences of head and neck squamous cell carcinoma(HNSCC)have been on the rise in the last few decades,with a significant risk factor being human papillomavirus(HPV)type-16/18 infection,particularly in the development of oropharyngeal cancers.Radiotherapy(RT)is an important treatment modality for HNSCC,where it promotes extensive cellular DNA damage leading to the therapeutic effect.It has been well-established that HPV-positive HNSCC display better response rates and improved survival following RT compared to HPV-negative HNSCC.The differential radiosensitivity has been largely associated with altered cellular DNA damage response mechanisms in HPV-positive HNSCC,and particularly with the signaling and repair of DNA double strand breaks.However,other factors,particularly hypoxia present within the solid cancer,have a major impact on relative radioresistance.Consequently,recent approaches aimed at enhancing the radiosensitivity of HNSCC have largely centered on targeting key proteins involved in DNA repair,DNA damage checkpoint activation,and hypoxia signaling.These studies have utilised in vitro and in vivo models of HPV-positive and HPV-negative HNSCC and examined the impact of specific inhibitors against the targets in combination with radiation in suppressing HNSCC cell growth and survival.Here,accumulating evidence has shown that targeting enzymes including poly(ADP-ribose)polymerase,ataxia telangiectasia and Rad-3 related,DNA-dependent protein kinase catalytic subunit,and checkpoint kinase 1 can radiosensitise HNSCC cells which should be taken forward in further preclinical studies,with the goal of optimizing the future effective RT treatment of HNSCC.
文摘In this work,the results of an experimental study of the impulse characteristic of practical ground electrodes consisting of horizontal conductors of various lengths and full-scale tower footings were reported.These electrodes were installed at an outdoor test site having nonuniform soil,with equipment facilities for generating low-and high-magnitude impulse currents.The tests on the horizontal electrode were used to determine the effective length,the voltage and current distribution along the electrode length and the effect of the injection point along the electrode.The tests on the tower footings were used to determine impulse resistance and demonstrate its non-linear variation with current magnitude.Computer simulations of the test electrodes using the electromagnetic field method showed good agreement with the measured result.
基金supported by the National Natural Science Foundation of China(21822107,21571115,21827801,21671172)the Natural Science Foundation of Shandong Province(JQ201803,ZR2017MB061)+2 种基金the Taishan Scholar Project of Shandong Province of Chinathe Qilu Youth Scholar Funding of Shandong Universitythe Fundamental Research Funds of Shandong University(104.205.2.5)
文摘The combination of CrO4^2-anion and N,N′-dimethylformamide(DMF)-containing solvent helps to stabilize an atom-precise ultrasmall Ag6 kernel into a 52-nuclei silver shell,giving a core-shell Ag6@Ag52 wheel-like structure(SD/Ag58b).The solution behavior and photocurrent response property were investigated in details.
文摘In the present study the first 20 microatoms of the periodic table are named as bioatoms, since they are needed for biochemical functions and services to life itself. The rationale behind this project is the detailed analysis of the ionization energy of the electrons in the inside of the bioatoms and their orderly arrangement at specific positions. Such position of the electrons is harmonized with the succession of their energy values in their logarithmic curves. The compelling arrangement of each electron at a particular place would not be feasible in the absence of an energy offset, which is a proton. The latter would hold electrons on their proper position. These fundamental aspects of our project receive such strong support from the quantum theory, according to which it is the electromagnetic interaction between electrons and protons by the exchange of photons, which hold them together in the atoms. According to our proposed model, the protons of the aforementioned proton—electron twins, are distributed on distinct positions which are the junctions of a primary network, coupled with their electrons, in a secondary network. The geometry and distance of the protons, in the plexus, is constant and is calculated at 8, 42 ?. This was estimated by a mathematical analysis of the proposed model, as discussed further. Our study has shown that electrons in the specific positions are moving in a symmetrical oscillation in the length of a channel, in vacuum, under the Coulomb forces. Moreover, the chemical evidence suggests that electrons, in an atom, have their own separate orbit, and that these orbits are closely interrelated.
