Irradiation of paranasal sinus tumors, a delineation and dose comparison study.

PURPOSE: To determine the influence of observer variation and treatment planner variation on the dose delivered to the target and normal structures when irradiating paranasal sinus carcinomas. PATIENTS AND METHODS: Nine patients with paranasal sinus tumors underwent debulking surgery and subsequent radiation therapy. Two observers from two different institutions delineated the clinical target volumes (CTVs) for the elective and the boost volumes. These volumes were expanded in three dimensions with a 5-mm margin. At both institutions, a three-dimensional conformal treatment plan of 46 Gy to the elective volumes, plus 20 Gy to the boost target volumes, was designed. The delineated volumes and treatment plans were compared. RESULTS: The mean volume ratio between institutions of the elective CTVs was 0.9 (standard error = 0.05). The differences were located mainly at the bottom of the nasal cavity and at the frontal border of the target areas. The differences in boost CTVs were large; the mean volume ratio was 2.6 (standard error = 0.58). After expansion of the CTV, the mean distance between the planning target volume (PTV) and the chiasm differed by 0.5 cm between the two institutions. Cases with smaller distances between the PTV and the chiasm had more underdosage to the PTV. This effect was less pronounced for institution A (1 vol.%/cm) than for institution B (10 vol.%/cm) treatment plans, which were less conformal. When the treatment plan was designed for the PTV of institution B, 23 volume % of the PTV of institution A received <95% of the prescribed dose. If the treatment plan was designed for the (on average larger) PTV of institution A, the underdosed volume of PTV at institution B was 17%. The relative underdosage to the "other" PTV was larger when the original treatment plan was more conformal. CONCLUSION: In the irradiation of paranasal sinus cancer, both the treatment planner and the observer have a significant influence on the dose to the target and organs at risk. Both effects are similar in magnitude. The observer effect increases with more conformal treatment plans. Minimizing the observer variation is important for adequate irradiation of paranasal sinus cancer.     

Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin

BACKGROUND: The role of dietary components in cancer progression and metastasis is an emerging field of clinical importance. Many stages of cancer progression involve carbohydrate-mediated recognition processes. We therefore studied the effects of high pH- and temperature-modified citrus pectin (MCP), a nondigestible, water-soluble polysaccharide fiber derived from citrus fruit that specifically inhibits the carbohydrate-binding protein galectin-3, on tumor growth and metastasis in vivo and on galectin-3-mediated functions in vitro. METHODS: In vivo tumor growth, angiogenesis, and metastasis were studied in athymic mice that had been fed with MCP in their drinking water and then injected orthotopically with human breast carcinoma cells (MDA-MB-435) into the mammary fat pad region or with human colon carcinoma cells (LSLiM6) into the cecum. Galectin-3-mediated functions during tumor angiogenesis in vitro were studied by assessing the effect of MCP on capillary tube formation by human umbilical vein endothelial cells (HUVECs) in Matrigel. The effects of MCP on galectin-3-induced HUVEC chemotaxis and on HUVEC binding to MDA-MB-435 cells in vitro were studied using Boyden chamber and labeling assays, respectively. The data were analyzed by two-sided Student's t test or Fisher's protected least-significant-difference test. RESULTS: Tumor growth, angiogenesis, and spontaneous metastasis in vivo were statistically significantly reduced in mice fed MCP. In vitro, MCP inhibited HUVEC morphogenesis (capillary tube formation) in a dose-dependent manner. In vitro, MCP inhibited the binding of galectin-3 to HUVECs: At concentrations of 0.1% and 0.25%, MCP inhibited the binding of galectin-3 (10 micro g/mL) to HUVECs by 72.1% (P =.038) and 95.8% (P =.025), respectively, and at a concentration of 0.25% it inhibited the binding of galectin-3 (1 micro g/mL) to HUVECs by 100% (P =.032). MCP blocked chemotaxis of HUVECs toward galectin-3 in a dose-dependent manner, reducing it by 68% at 0.005% (P<.001) and inhibiting it completely at 0.1% (P<.001). Finally, MCP also inhibited adhesion of MDA-MB-435 cells, which express galectin-3, to HUVECs in a dose-dependent manner. CONCLUSIONS: MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.     

Effects of euthanasia on brain physiological activities monitored in real-time

Animal experimentation is terminated by the euthanasia procedure in order to avoid pain and minimize suffering. Very little is known about the real time physiological changes taking place in the brain of animals during the euthanasia. Since there is no way to evaluate the suffering of animals under euthanasia, it is assumed that objective physiological changes taking place could serve as a good way to compare various types of euthanasia procedures. In the present study we compared the effect of euthanasia induced by i. v. injection of concentrated KCL to that of Taxan T-61 (a standard mixture used by veterinarians). The responses of the cat brain were evaluated by monitoring the hemodynamic (CBF), metabolic (NADH redox state), electrical (EcoG) and extracellular ion levels, as an indicator to the ionic homeostasis.     

Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity

This study examined the expression of constitutive endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) in the sciatic nerve of Lewis rats with experimental autoimmune neuritis (EAN). Western blot analysis showed that both eNOS and iNOS expressions in the sciatic nerves of rats increased significantly during the peak stage of EAN, but declined thereafter. Only minimal amounts of these enzymes were identified in normal rat sciatic nerves. Immunohistochemical studies showed that eNOS was increased in vascular endothelial cells and Schwann cells, but not in inflammatory cells, during the peak stage of EAN. However, iNOS was found mainly in inflammatory macrophages in sciatic nerve EAN lesions.These findings suggest that, depending on the stage of peripheral nervous system autoimmune disease, the increased expressions of both eNOS and iNOS might be involved in either the production of detrimental effects during the induction stage of EAN or in the recovery from EAN paralysis.     

Auditory and vestibular mouse mutants: models for human deafness

We have shown here several examples of how hearing and vestibular impaired mouse mutants are generated and the insight that they provide in the study of auditory and vestibular function. These types of genetic studies may also lead to the identification of disease-susceptibility genes, perhaps the most critical element in presbyacusis (age-related hearing loss). Some individuals may be more prone to hearing loss with increasing age or upon exposure to severe noise, and susceptibility genes may be involved. Different inbred mice show a variety of age-related and noise-induced hearing loss that varies between normal hearing and severe deafness throughout their life span /27/. Genetic diversity between inbred mouse strains has been shown to be a powerful tool for the discovery of modifier genes. Already two studies have found regions in which modifier genes for deafness may reside /28-29/. Future studies will hopefully lead to the identification of genes that modify hearing loss and will help us understand the variability that exists in human hearing, a crucial component in developing successful treatment strategies. The first human non-syndromic deafness-causing gene was identified in 1995, and since then, additional genes have been discovered. Much of the credit for this boom is due to deaf and vestibular mouse mutants. Their study has led to great insight regarding the development and function of the mammalian inner ear, and correlations with human deafness can now be made since mutations in the same genes have been found in these two mammals. As deafness is the most common form of sensory impairment and affects individuals of all ages, elucidating the function of the auditory and vestibular systems through genetic approaches is essential in improving and designing effective treatments for hearing loss.     

Carbohydrate-Recognition and Angiogenesis

Angiogenesis is required for the continual growth of the tumor and provides a gateway for cells to escape the confines of the primary tumor. Angiogenic stimulus triggers a cascade of functional responses leading to local basement membrane dissolution, endothelial cell migration, proliferation and microvessel morphogenesis. In this commentary, we review the significance of carbohydrate-binding proteins involved in angiogenesis. The importance of carbohydrate-recognition processes to angiogenesis stems from the observation that angiogenic factors like fibroblast growth factor family and vascular endothelial growth factors bind initially to the extracellular matrix proteoglycans before binding to their cognate receptors, and some of the adhesion molecules bind to glycoconjugates present on the surface of the endothelial cells. The possible significance of these interactions will be discussed.     

A New Optical Technique for Evaluating Collective Motility of Ram and Bull Ejaculated Spermatozoa

A new. non-destructive, objective technique for measuring collective motility of highly-concentrated ram and bull semen is described. The principle is based on changes in the reflected light scattered by motile spermatozoa. These changes can be recorded as a continuous analog wave pattern (Reflectospermiogram-RSG) and are correlated to the intensity of the turbulent motility as evaluated subjectively with an ordinary light microscope. Ram spermatozoa have, after ejaculation, a typical motility pattern, i.e., high, stable activity for about 20 min, then a period during which the motility decreases at a constant rate, and finally, a period with a low but rather constant activity. The usefulness of the technique has been demonstrated in various types of experiments.