An attempt made to construct a model of relationship of the radioprotective and carcinogenic properties of biologically active compounds with their electron and information factors. We discovered a simple quantitative...An attempt made to construct a model of relationship of the radioprotective and carcinogenic properties of biologically active compounds with their electron and information factors. We discovered a simple quantitative structure – activity relationships between the radioprotective effectiveness of chemicals and their molecular structure. It is established that carcinogenic properties of chemical compounds and effective radioprotectors are overlapping with each other. Within the framework of an information approach a systemic factor is proposed for distinguish highly radio protective agents among a series of drug. It was shown that the correlation obtained relating the structure of the compounds of the radio protective effect may be applied to studies of the mechanism of action of the preparations and for the purposeful synthesis of new chemicals.展开更多
Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in anim...Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.展开更多
AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or seve...AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.METHODS: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo(95%CI: 3.3-21.5).CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.展开更多
AIM: To investigate whether selenomethionine(SLM) reduces mucositis incidence in patients with head and neck squamous cell cancer(HNSCC) undergoing concurrent chemoradiation(CRT).METHODS: In this multi-institutional, ...AIM: To investigate whether selenomethionine(SLM) reduces mucositis incidence in patients with head and neck squamous cell cancer(HNSCC) undergoing concurrent chemoradiation(CRT).METHODS: In this multi-institutional, randomized, double-blind phase Ⅱ trial, patients with Stage Ⅲ or Ⅳ HNSCC received SLM 3600 μg/m2 or placebo twice daily for 7 d prior to CRT, once daily during CRT, and daily for 3 wk following CRT. CRT consisted of 70 Gy at 2 Gy per fraction with cisplatin 100 mg/m2 Ⅳ on days 1, 22, and 43. RESULTS: Eighteen patients were randomized, 10 received SLM, and there were no differences in baseline factors. There was no difference in mucositis or patientreported side effects between groups. There was no difference in overall or relapse-free survival at 12 mo.CONCLUSION: Addition of SLM to CRT for HNSCC was well-tolerated but did not lower the incidence of severe mucositis or improve quality of life or survival outcomes.展开更多
Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Recently, there has been an increase in the interest in research...Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Recently, there has been an increase in the interest in research on synthetic and/or natural radioprotective agents. An important potential use for these agents is to modify and improve the outcome of radiation therapy. The aim of this study was to examine the potential radioprotective role and antioxidant potency of the novel synthetic anticancer agent, quinoline sulfonamide (PIQSA) against tissue injury and oxidative stress induced by the exposure to gamma radiation and/or incidence of cancer in experimental animals. Mice (normal and bearing solid tumors) administered PIQSA (0.350 mg/kg body weight ip. three times a week for 21 days. At the last week of 30 days experimental period, an animal group was subjected to three successive doses of γ-radiation each of 2 Gy;another group was treated with combined administration of PIQSA 20 minutes before γ-irradiation. Some biochemical parameters (LPx, GSH, SOD, and CAT in liver homogenates, also plasma lipid profile (total lipids, total cholesterol, total triglycerides (TG), HDLc and LDLc were measured. To examine any adverse effect which could be attained by chemical treatment, liver enzymes (AST, ALT), and kidney function (creatinine and urea) were estimated in blood plasma, in addition to examination of some haematological indexes. The results indicated that the deleterious effects due to exposure to γ-radiation, and/or incidence of cancer on most of the estimated parameters could be controlled to a certain extent by administration of PIQSA to animals prior to irradiation. The results also confirmed that there were no significant adverse effects on mice due to the treatment with this chemical compound.展开更多
文摘An attempt made to construct a model of relationship of the radioprotective and carcinogenic properties of biologically active compounds with their electron and information factors. We discovered a simple quantitative structure – activity relationships between the radioprotective effectiveness of chemicals and their molecular structure. It is established that carcinogenic properties of chemical compounds and effective radioprotectors are overlapping with each other. Within the framework of an information approach a systemic factor is proposed for distinguish highly radio protective agents among a series of drug. It was shown that the correlation obtained relating the structure of the compounds of the radio protective effect may be applied to studies of the mechanism of action of the preparations and for the purposeful synthesis of new chemicals.
基金supported by the Nuclear Research and Development Program(NRF-2012M2A2A7012377,NRF-2015M2B2B1068627 and NRF-2015R1C1A2A01053041)of the National Research Foundation of Korea(NRF)funded by the Korean Government Ministry of Science,ICT&Future Planning
文摘Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016.
基金Supported by The Health Research Council of New Zealand
文摘AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine(SLM) with concurrent chemoradiation(CCRT) for Stage Ⅲ non-small cell lung cancer(NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.METHODS: Sixteen patients with stage Ⅲ NSCLC were accrued to this single arm, phase Ⅱ study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly Ⅳ paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment. RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients(19%), pneumonitis in 0, leukopenia in 2(12.5%), and anemia in 1(6%); the latter two were significantly reduced when compared to the protocolstated expected rate of 35%(P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo(95%CI: 3.3-21.5).CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.
基金Supported by A grant from the Health Research Council of New Zealand(in part)
文摘AIM: To investigate whether selenomethionine(SLM) reduces mucositis incidence in patients with head and neck squamous cell cancer(HNSCC) undergoing concurrent chemoradiation(CRT).METHODS: In this multi-institutional, randomized, double-blind phase Ⅱ trial, patients with Stage Ⅲ or Ⅳ HNSCC received SLM 3600 μg/m2 or placebo twice daily for 7 d prior to CRT, once daily during CRT, and daily for 3 wk following CRT. CRT consisted of 70 Gy at 2 Gy per fraction with cisplatin 100 mg/m2 Ⅳ on days 1, 22, and 43. RESULTS: Eighteen patients were randomized, 10 received SLM, and there were no differences in baseline factors. There was no difference in mucositis or patientreported side effects between groups. There was no difference in overall or relapse-free survival at 12 mo.CONCLUSION: Addition of SLM to CRT for HNSCC was well-tolerated but did not lower the incidence of severe mucositis or improve quality of life or survival outcomes.
文摘Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Recently, there has been an increase in the interest in research on synthetic and/or natural radioprotective agents. An important potential use for these agents is to modify and improve the outcome of radiation therapy. The aim of this study was to examine the potential radioprotective role and antioxidant potency of the novel synthetic anticancer agent, quinoline sulfonamide (PIQSA) against tissue injury and oxidative stress induced by the exposure to gamma radiation and/or incidence of cancer in experimental animals. Mice (normal and bearing solid tumors) administered PIQSA (0.350 mg/kg body weight ip. three times a week for 21 days. At the last week of 30 days experimental period, an animal group was subjected to three successive doses of γ-radiation each of 2 Gy;another group was treated with combined administration of PIQSA 20 minutes before γ-irradiation. Some biochemical parameters (LPx, GSH, SOD, and CAT in liver homogenates, also plasma lipid profile (total lipids, total cholesterol, total triglycerides (TG), HDLc and LDLc were measured. To examine any adverse effect which could be attained by chemical treatment, liver enzymes (AST, ALT), and kidney function (creatinine and urea) were estimated in blood plasma, in addition to examination of some haematological indexes. The results indicated that the deleterious effects due to exposure to γ-radiation, and/or incidence of cancer on most of the estimated parameters could be controlled to a certain extent by administration of PIQSA to animals prior to irradiation. The results also confirmed that there were no significant adverse effects on mice due to the treatment with this chemical compound.
