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排序方式: 共有1610条查询结果,搜索用时 15 毫秒
91.
Greenberger JS Kagan VE Pearce L Boriseniao G Tyurina Y Epperly MW 《Antioxidants & redox signaling》2001,3(3):347-359
Reactive oxygen species (ROS)-mediated damage to DNA is associated with induction of stress-activated protein kinases leading to secondary and tertiary effects on the nuclear matrix, cytoplasmic transport mechanisms, and altered mitochondrial and cell membranes. The cellular defenses against ROS damage are associated with up-regulation of gene products that can significantly alter cell biology, including antiapoptotic Bax family proteins and inflammatory proteins. Altered cell integrity can occur either directly or by indirect paracrine and juxtacrine interactions within tissues. Previous approaches toward therapeutic intervention against ROS damage have included administration of radical scavenger compounds, use of novel drugs that increase cellular production of constitutive antioxidants, or pharmacologic agents that modify the intracellular transport of antioxidants. Strategies to modify the cellular effects of ROS in hyperbaric oxygen injury to the lung, reperfusion injury to transplanted organs, and cancer have led to novel approaches of gene therapy in which the transgenes for antioxidant proteins can be expressed in specific tissues. Reducing tissue-damaging effects of ROS may have relevance to cancer patients by ameliorating normal tissue damage from ionizing irradiation therapy, photodynamic therapy, and cancer chemotherapy. 相似文献
92.
Kagan E 《Clinics in Laboratory Medicine》2001,21(3):607-18, ix-x
Bioregulators are naturally occurring organic compounds that regulate diverse cellular processes. Unlike traditional disease-causing biowarfare agents that take hours or days to act, many bioregulators act within minutes of administration. If exploited for the purpose of bioterrorism, they could potentially cause profound physiologic effects. Other effects may be more subtle. The main groups of bioregulators discussed are cytokines; eicosanoids, neurotransmitters, hormones, and proteolytic enzymes. Because advances continually are being made in their development, bioregulators should be considered as weapons with increasing bioterrorism potential. 相似文献
93.
Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation 总被引:2,自引:0,他引:2
Epperly MW Kagan VE Sikora CA Gretton JE Defilippi SJ Bar-Sagi D Greenberger JS 《International journal of cancer. Journal international du cancer》2001,96(4):221-231
Intraesophageal administration of manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) prior to single fraction radiation has been shown to protect mice from lethal esophagitis. In our study, C3H/HeNsd mice received fractionated radiation in two protocols: (i) 18 Gy daily for four days with MnSOD-PL administration 24 hr prior to the first and third fraction, or (ii) 12 Gy daily for six days with MnSOD-PL 24 hr prior to the first, third, and fifth fraction. Control radiated mice received either no liposomes only or LacZ (bacterial beta-galactosidase gene)-plasmid/liposome (LacZ-PL) by the same schedules. We measured thiol depletion and lipid peroxidation (LP) in whole esophagus and tested the effectiveness of a new plasmid, hemagglutinin (HA) epitope-tagged MnSOD (HA-MnSOD). In fractionation protocols, mice receiving MnSOD-PL, but not LacZ-PL (200 microl of plasmid/liposomes containing 200 microg of plasmid DNA), showed a significant reduction in morbidity, decreased weight loss, and improved survival. Four and seven days after 37 Gy single fraction radiation, the esophagus demonstrated a significant increase in peroxidized lipids and reduction in overall antioxidant levels, reduced thiols, and decreased glutathione (GSH). These reductions were modulated by MnSOD-PL administration. The HA-MnSOD plasmid product was detected in the basal layers of the esophageal epithelium 24 hr after administration and provided significant radiation protection compared to glutathione peroxidase-plasmid/liposome (GPX-PL), or liposomes containing MnSOD protein, vitamin E, co-enzyme Q10, or 21-aminosteroid. Thus, MnSOD-PL administration significantly improved tolerance to fractionated radiation and modulated radiation effects on levels of GSH and lipid peroxidation (LP). These studies provide further support for translation of MnSOD-PL treatment into human esophageal radiation protection. 相似文献
94.
After the initiation of androgen suppression in men with prostate cancer, the serum prostate-specific antigen (PSA) level generally declines. A subsequent PSA rise during that suppression usually reflects the presence of a significant component of hormonally refractory prostate cancer. We report a patient with a rising PSA level and elevated testosterone level after depot leuprolide in whom the PSA level subsequently declined with administration of bicalutamide. 相似文献
95.
96.
R W Lange B W Day R Lemus V A Tyurin V E Kagan M H Karol 《Chemical research in toxicology》1999,12(10):931-936
Diisocyanatotoluene (toluene diisocyanate, TDI), a 4:1 mixture of 2, 4- and 2,6-isomers used in the preparation of polyurethanes, causes occupational asthma by an as yet unknown mechanism. We previously showed that it forms adducts with the apical surface of the bronchoepithelium in vivo, and with ciliary microtubules in cultured human bronchoepithelial (HBE) cells. These results suggested that TDI may not enter HBE cells. In vitro studies, however, showed that TDI avidly forms bis adducts with glutathione (GSH) and that these adducts transfer monoisocyanato-monoglutathionyl-TDI to a sulfhydryl-containing peptide. This study sought to elucidate intracellular reactions of TDI. Using an electron paramagnetic resonance spectrometric (EPR) method, we established that the level of thiol-dependent quenching of phenoxyl radicals of etoposide was decreased >40% in pulmonary tissue of mice that received TDI intrabronchially. Similarly, HBE cells exposed to 100 ppb TDI vapor experienced a >30% reduction in thiol levels as determined with a thiol-specific fluorescent probe (ThioGlo 1). HPLC/UV analysis of lysates from HBE cells exposed to 200 and 500 ppb TDI vapor suggested a dose-related formation of S-glutathionyl adducts. Data from the 500 ppb TDI-treated HBE cells verified the identity of the 2-monoglutathionyl-4-monoisocyanato adduct. The results provide firm evidence that TDI enters pulmonary cells and reacts with GSH. This rapid reaction leading to formation of S-glutathionyl adducts of TDI suggests the importance of cellular thiols in TDI-induced pulmonary disease. 相似文献
97.
Spitz MR Strom SS Yamamura Y Troncoso P Babaian RJ Scardino PT Wheeler T Amos CI von Eschenbach A Kagan J 《International journal of cancer. Journal international du cancer》2000,89(3):259-264
While tumor volume and Gleason scores are the best available prognostic indicators for prostate cancer, contemporary predictive methods are unable to identify which men with Gleason scores of 7 have clinically insignificant tumors that will not progress and which men will develop highly aggressive prostate cancer. Our objective was to evaluate potential environmental determinants of significant prostate cancer. Subjects were patients identified from a university-based hospital and tertiary cancer center who had undergone radical prostatectomy for prostate cancer. Cases were 103 patients whose tumor volumes were =0.5 ml. The comparison group was comprised of 225 men with larger-volume disease or with histologic evidence of extracapsular extension but without lymph node involvement. The matching criteria were ethnicity, age at diagnosis (+/-5 years), and date of diagnosis (+/-1 year). Epidemiologic data, current weight, and height were obtained. The comparison group was significantly more likely than cases to be current smokers (7.6% vs. 3.9%) and to report more pack-years smoked (30.1 vs. 23.0 years, p = 0.06). Cases tended to weigh less (85.2 vs. 87.1 kg, p = 0.1) and have lower body mass indices (26.8 vs. 27.6, p = 0.07). A similar trend was evident for weight at age 40 (79 vs. 81 kg). Cases reported a mean weight gain of 4.9 kg compared with 6. 6 kg in the comparison subjects (p = 0.05) between the ages of 25 and 40. There was no significant difference in weight gain from age 40 to current age. Cases were more likely to report having prostate cancer screening (90% vs. 80%, p = 0.02). Cases with Gleason scores =7 (3 + 4, with 3 being the dominant grade) were younger at diagnosis than those with scores of 7 (4 + 3, with 4 being the dominant grade), were more likely (93%) to have had prostate screening, were less likely to be current smokers (4%), reported the fewest pack-years smoked (21.5 vs. 28.6 years for high-score cases and 30.1 for comparison subjects), and had the lowest average weight gain from ages 25 to 40 (4.62 vs. 6.31 kg for high-score cases). Weight gain in early adulthood and smoking thus appear to be important predictors of virulent prostate cancer. Our data also suggest that prior screening is associated with diagnosis of lower-volume and lower-score disease. 相似文献
98.
99.
Nano‐sized materials and nano‐scaled processes are widely used in many industries. They are being actively introduced as diagnostic and therapeutic in biomedicine and they are found in numerous consumer products. The small size of nanoparticles, comparable with molecular machinery of cells, may affect normal physiological functions of cells and cause cytotoxicity. Their toxic potential cannot be extrapolated from studies of larger particles due to unique physicochemical properties of nanomaterials. Therefore, the use of nanomaterials may pose unknown risks to human health and the environment. This review discusses several important issues relevant to pulmonary toxicity of nanoparticles, especially single‐walled carbon nanotubes (SWCNT), their direct cytotoxic effects, their ability to cause an inflammatory response, and induce oxidative stress upon pharyngeal aspiration or inhalation. Further, recognition and engulfment of nanotubes by macrophages as they relate to phagocytosis and bio‐distribution of nanotubes in tissues and circulation are discussed. The immunosuppressive effects of CNT and their significance in increased sensitivity of exposed individuals to microbial infections are summarized. Finally, data on biodegradation of SWCNT by oxidative enzymes of inflammatory cells are presented in lieu of their persistence and distribution in the body. 相似文献
100.