Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that frequently metastasizes and that overexpresses transforming growth factor-beta s (TGF-beta s). To determine whether TGF-beta s can act to enhance the metastatic potential of PDAC, PANC-1 human pancreatic cancer cells were transfected with an expression construct encoding a soluble type II TGF-beta receptor (sT beta RII) that blocks cellular responsiveness to TGF-beta 1. When injected s.c. in athymic mice, PANC-1 clones expressing sT beta RII exhibited decreased tumor growth in comparison with sham-transfected cells and attenuated expression of plasminogen activator inhibitor 1 (PAI-1), a gene associated with tumor growth. When tested in an orthotopic mouse model, these clones formed small intrapancreatic tumors that exhibited a suppressed metastatic capacity and decreased expression of plasminogen activator inhibitor 1 and the metastasis-associated urokinase plasminogen activator. These results indicate that TGF-beta s act in vivo to enhance the expression of genes that promote the growth and metastasis of pancreatic cancer cells and suggest that sT beta RII may ultimately have a therapeutic benefit in PDAC. 相似文献
Previous studies documented the effectiveness and benefits of capnography monitoring during propofol-based sedation for colonoscopy to reduce the incidence of hypoxemia. However, the performance of capnography during longer duration endoscopic therapy of upper gastrointestinal tract cancers under CO2 insufflation it is not well known. In this study, we compare a new device with acoustic monitoring technology to standard capnography monitoring. We retrospectively analyzed 49 patients who underwent endoscopic resection of early upper gastrointestinal tract cancer between December 2013 and October 2014. All 49 patients were monitored using both acoustic monitoring technology and standard capnography. We investigated the duration of the periods with unmeasurable respiratory rate during the overall procedure. When comparing standard capnography monitoring to the new acoustic monitoring technology, the ratio of the unmeasurable time was significantly lower in RRa (36.9% vs. 21.6%, p?<?0.01). The ratio of unmeasurable respiratory rate by capnography was strongly correlated to the ratio of unmeasurable PetCO2 level by capnography (R2?=?0.847). There were no severe events or adverse events (grade 2 or more) during all 49 procedures. The acoustic monitoring technology provides a more reliable respiratory monitoring when compared to standard capnography during endoscopic resection of upper gastrointestinal tract cancers under CO2 insufflation, even if the procedures were prolonged and complex.
"Nanoparticle" is defined as the particles whose diameter in at least one dimension is less than 100 nm. Compared with fine-particles, nanoparticles have large specific surface area. There is a dramatic increase over fine-particles in chemical and physical activities, such as ion release, adsorption ability, and ROS production. These properties are important for industrial use, and many nanoparticles are already used in products familiar to consumers as sunscreens and cosmetics. However, nanoparticle properties beneficial to the industry may also induce biological influences, including toxic activities. Recently, many investigations about the toxicology of nanoparticles have been reported. In the evaluation of nanoparticles toxicity, in vitro studies give us important information, especially in terms of toxic mechanisms. In vitro studies showed that some nanoparticles induce oxidative stress, apoptosis, production of cytokines, and cell death. There are reports that cellular influences of other nanoparticles are small. There are also reports of different results, some with low and some with high influences, for the same nanoparticle. One of the causes of this inconsistency might be a diremption of the living body influence study and the characterization study. Characterization of individual nanoparticles and their dispersions are essential for in vitro evaluation of their biological effects since each nanoparticle shows unique chemical and physical properties. Particularly, the aggregation state and metal ion release ability of nanoparticles affect its cellular influences. Reports concerning the characterization in the in vitro toxicity assessment are increasing. For an accurate risk assessment of nanoparticles, in this review, we outline recent studies of in vitro evaluation of cellular influences induced by nanoparticles. Moreover, we also introduce current studies about the characterization methods of nanoparticles and their dispersions for toxicological evaluation. 相似文献
Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic (DA) neuronal cell loss in the substantia nigra. Although the entire pathogenesis of PD is still unclear, both environmental and genetic factors contribute to neurodegeneration. Epidemiologic studies show that prevalence of PD is lower in smokers than in nonsmokers. Nicotine, a releaser of dopamine from DA neurons, is one of the candidates of antiparkinson agents in tobacco. To assess the protective effect of nicotine against rotenone-induced DA neuronal cell toxicity, we examined the neuroprotective effects of nicotine in rotenone-induced PD models in vivo and in vitro. We observed that simultaneous subcutaneous administration of nicotine inhibited both motor deficits and DA neuronal cell loss in the substantia nigra of rotenone-treated mice. Next, we analyzed the molecular mechanisms of DA neuroprotective effect of nicotine against rotenone-induced toxicity with primary DA neuronal culture. We found that DA neuroprotective effects of nicotine were inhibited by dihydro-beta-erythroidine (DHbetaE), alpha-bungarotoxin (alphaBuTx), and/or PI3K-Akt/PKB (protein serine/threonine kinase B) inhibitors, demonstrating that rotenone-toxicity on DA neurons are inhibited via activation of alpha4beta2 or alpha7 nAChRs-PI3K-Akt/PKB pathway or pathways. These results suggest that the rotenone mouse model may be useful for assessing candidate antiparkinson agents, and that nAChR (nicotinic acetylcholine receptor) stimulation can protect DA neurons against degeneration. 相似文献
OBJECTIVES: To investigate the association between ambulatory blood pressure (BP) variables (level, short-term variability, circadian variation and morning pressor surge) and carotid artery alteration in a general population. METHODS: We measured ambulatory BP every 30 min in 775 participants (mean age 66.2 +/- 6.2 years, 68.8% women) from the Japanese general population. Short-term BP variability during the daytime and night-time were estimated as within-subject standard deviation of daytime and night-time BP, respectively. Circadian BP variation was calculated as the percentage decline in nocturnal BP. Morning pressor surge was defined as morning BP minus pre-waking BP. The extent of carotid artery alteration was evaluated as the average of common carotid intima-media thickness (IMT) and the presence of focal carotid plaque. RESULTS: Daytime and night-time BP values were more closely associated with carotid artery alteration than casual BP. With mutual adjustment for daytime and night-time BP, the latter (P < 0.0001) was more closely associated with IMT, which represents diffuse arterial thickening and arteriosclerosis, than daytime BP (P = 0.2). Night-time systolic BP variability was positively associated with carotid plaque (focal atherosclerotic lesions) independently of possible confounding factors, including night-time systolic BP (P = 0.01). A diminished nocturnal decline in systolic BP was associated with a greater IMT after adjustment for confounding factors (P = 0.03). A morning pressor surge was not associated with carotid artery alteration. CONCLUSION: Ambulatory BP levels and BP variability were closely associated with carotid artery alteration, suggesting that these parameters are independent risk factors or predictors of carotid artery alteration. 相似文献