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      • KCI등재후보

        Nicotine and Ethanol Modulation of Cell-mediated Immune Surveillance of Oral Squamous Cell Carcinoma

        Chiappelli, Francesco,Kung, Michelle A.,Savage, Mason,Villanueva, Pablo,Fiala, Milan Korean Academy of Oral Biology and the UCLA Dental 1996 International Journal of Oral Biology Vol.21 No.1

        Tobacco and alcohol are major contributing factors in the carcinogenesis of oral epithelium. We tested the hypothesis that nicotine and ethanol, at concentrations approximating those found in the plasma of smokers and alcohol abusers, decrease immune surveillance of oral carcinoma by interfering with immune cell-mediated clearance of the tumor targets. Specifically, we have examined the modulation by nicotine and ethanol of the migration of normal human immune cells to activation, and their cytolytic ability. To assess migration, we tested the ability of activated peripheral blood mononuclear cells to adhere and to migrate to a given squamous cell carcinoma of the tongue, using a construct consisting of a monolayer of human neural endothelial cells growing over a porous membrane through which lymphocytes migrate in order to attain the tumor target cells. Adhesion and transmigration through the construct was visualized by electron microscopy. The T cells' ability to bind to the target tumor was assessed by immunocytobiochemistry. T cell activation was assessed as blast cell formation and thymidine incorporation following stimulation. Cytolytic immune cells activity was tested by quantification of specific killing of target cells. We show a diminution of migration, binding, activation and cytotoxic activity by nicotine when coupled with ethanol. Spontaneous cell death was not induced by nicotine and ethanol, when monitored as the release of cytoplasmic histone-associated DNA fragments in the cytoplasmic compartment. Taken together, our results indicate that the modulation of tumor cell-mediated immune surveillance in vitro by nicotine alone is modest, and that it exacerbates the effects of ethanol.

      • KCI등재후보

        Non-Mammalian Models of Neuroendocrine-Immune Modulation : Relevance for Research in Oral Biology and Medicine

        Chiappelli, Francesco,Liu, Nancy Korean Academy of Oral Biology and the UCLA Dental 1999 International Journal of Oral Biology Vol.24 No.2

        Physiological processes are remarkably well conserved through evolution, and finely modulate the vast array of immune responses, which, taken together, constitute immune surveillance. The neuroendocrine system, including catecholaminergic, cholinergic and vagal innervation as well as the endogenous opioid, the pro-opiomelanocortin and other families of peptides, steroid and other hormones, play a significant role in modulating the cellular, biochemical and molecular pathways that direct and regulate immune surveillance. Immune responses control and contain the spectrum of pathologies of the oral cavity, as well as their systemic sequelae. Non-mammalian organisms exhibit physiological responses similar to those of mammals, and thus provide reliable and simple animal models for targeted research in the domain of oral biology and medicine, Fish in particular provide simple, economic and reliabel non-mammalian systems to characterize and to define neuroendocrine-immune modulatory pathways, and to test well-defined experimental manipulations for the development of novel therapeutic interventions and the refinement of existing ones.

      • KCI등재후보

        The Role of the Tonsils in Oral Immune Surveillance

        Chiappelli, Francesco,Romeo, Horacio Korean Academy of Oral Biology and the UCLA Dental 2001 International Journal of Oral Biology Vol.26 No.1

        Basic science research has clearly demonstrated the teleological relevance of the tonsils by producing evidence in support of the critical role these structures play both as a key immune gate-keeper in the oral cavity, and in communicating to the central nervous system that a local immune response has been initiated and must be modulated by the brain. By contrast, clinical practice often recommends the surgical resection of the tonsils, suggesting tonsillectomy has no counter productive effect on the immune system, despite studies that may indicate the opposite. This paper reviews our fundamental and clinical knowledge of the tonsils.

      • KCI등재후보

        Experimentally-Induced Oral Cancer in the F344 Rat : Effect of Stress Exposure

        Hodgson, Deborah M.,Chiappelli, Francesco,Taylor, Anna N. Korean Academy of Oral Biology and the UCLA Dental 2000 International Journal of Oral Biology Vol.25 No.1

        Oral cancer(OC) is associated with diffuse mucosal abnormalities resulting from carcinogen exposure. The major carcinogens are alcohol and tobacco, however, diet and viral infections are also risk factors. More recently it has been reported that disruption to the hypothalamic-pituitary-adrenal(HPA) axis, causing hypercortisolaemia may be a major risk factor. Exposure to chronic stress is associated with hypercortisoleamia. In this study we examined the effect of exposure to a chronic stressor on mortality rates from lingual carcinoma induced by administration of the carcinogen 7.12-dimethylbenz〔a〕anthracene 〔DMBA〕in the Fisher 344〔F344〕rat. F344 rats, 60-day old, received an injection of DBMA 〔5mg/kg〕in the left lateral border of the middle third of the tongue. half of the animals were then subjected to "cold water swim stress" 〔2℃〕for 3×3 minutes five days/wk for three weeks. Survival at 20wks post injecting was the outcome measure. Exposure to the stress protocol was found to increased mortality by 20.6%. Exposure to stress was also shown to significantly increase plasma corticosterone levels〔p<0.001〕and decrease body weight〔p=0.05〕. As such, the present study suggests that chronic stress reduces the survival rate in animals with lingual cancer induced by the carcinogen DBMA. The increase in mortality is associated with increased corticosterone levels, but at this point it is not clear if this relationship is causal. Ongoing studies are investigating the nature of this relationship and the interactive nature of stress with other factors known to act as cancer promoters〔i.e., viral infection, alcohol and drug abuse, and carcinogen exposure〕.

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