Histamine modulates cellular events involved in tumour invasiveness in pancreatic carcinoma cells

Inflammation Research - .     

Feasibility of cranio-spinal axis radiation with the Hi-Art tomotherapy system.

BACKGROUND AND PURPOSE: Helical tomotherapy can eliminate the need for junction lines. The goal of this study is to evaluate tomotherapy in the delivery of CSA radiation and measurement of plan quality using physical parameters in comparing conventional (CSA-RT) and helical tomotherapy (CSA-TOMO) plans. PATIENTS AND METHODS: CSA-TOMO and CSA-RT plans were created for dosimetric comparison. Integral dose values were calculated. The ratios D50% (dose received by 50% of the organ at risk's volume) and D10% (dose received by 10% of the organ at risk's volume) were calculated representing large volumes and small volumes of organs at risk receiving significant dose. RESULTS: When considering D50% and D10%, CSA-TOMO has a dosimetric advantage over CSA-RT for most organs at risk. The body integral dose was higher for the CSA-TOMO plan by approximately 6.5%. CONCLUSIONS: Tomotherapy is a feasible alternative for treatment of CSA. Analysis shows that tomotherapy improves dose ratios over conventional radiation for most organs at risk. The impact of a small increase in whole body integral dose is unknown. Long-term follow-up will be needed to answer this question as others have argued of the possibility of increased risk of secondary malignancies due to delivery of radiotherapy with IMRT.     

Involvement of IL-1beta in acute stress-induced worsening of cerebral ischaemia in rats.

Stress is known to be one of the risk factors of stroke. Most of the knowledge on the effects of stress on cerebrovascular disease in humans is restricted to catecholamines and glucocorticoids effects on blood pressure and/or development of atherosclerosis. However, few experimental studies have examined the possible mechanisms by which stress may affect stroke outcome. We have used an acute stress protocol consisting of the exposure of male Fischer rats to an acute, single exposure immobilisation protocol (6 h) prior to permanent middle cerebral artery occlusion (MCAO), and we have found that stress worsens behavioural and neurological outcomes and increased infarct size after MCAO. The possible regulatory role of the TNFalpha and IL-1beta was studied by looking at the release of these cytokines in brain. The results of the present study showed an increase in IL-1beta release in cerebral cortex after exposure to acute stress. Brain levels of IL-1beta are also higher in previously stressed MCAO rats than in MCAO animals without stress. Pharmacological blockade of IL-1beta with an antibody anti-IL-1beta led to a decrease in the infarct size as well as in neurological and behavioural deficits after MCAO. In summary, our results indicate that IL-1beta, but not TNFalpha, accounts at least partly for the worsening of MCAO consequences in brain of rats exposed to acute stress.     

Influence of hospital characteristics on operative death and survival of patients after major cancer surgery in Ontario.

BACKGROUND: There is a lack of information from Canadian hospitals on the role of hospital characteristics such as procedure volume and teaching status on the survival of patients who undergo major cancer resection. Therefore, we chose to study these relationships using data from patients treated in Ontario hospitals. METHODS: We used the Ontario Cancer Registry from calendar years 1990-2000 to obtain data on patients who underwent surgery for breast, colon, lung or esophageal cancer or who underwent major liver surgery related to a cancer diagnosis between 1990 and 1995 in order to assess the influence of volume of procedures and teaching status of hospitals on in-hospital death rate and long-term survival. For each disease site and before observing patient outcomes data, volume cut-off points were selected to create volume groups with similar numbers of patients. Teaching hospitals were those directly affiliated with a medical school. Logistic regression and proportional hazards models were used to consider the clustering of data at the hospital level and to assess operative death and long-term survival. We also used 4 measures to gauge the degree of procedure regionalization across the province including (1) the number of hospitals performing a procedure; (2) the percentage of patients treated in teaching hospitals; (3) the percentage of rural patients treated in higher volume procedure hospitals; and (4) median distances travelled by patients to receive care. RESULTS: The number of patients in our cohorts who underwent resection of the breast, colon, lung, esophagus or liver was 14 346, 8398, 2698, 629 and 362, respectively. Surgery in a high-volume versus a low-volume hospital did not have a statistically significant influence on the odds of operative death for patients who underwent colon, liver, lung or esophageal cancer resection. The risk of long-term death was increased in low-volume versus high-volume hospitals for patients who underwent resection of the breast (hazard ratio [HR] 1.2, 95% confidence interval [95% CI] 1.0-1.4, p < 0.05), lung (HR 1.3, 95% CI 1.1-1.6, p < 0.01) and liver (HR 1.7, 95% CI 1.0-2.7, p = 0.04). There were no significant differences in the odds of operative (in-hospital) death or risk of long-term death among patients treated in teaching compared with nonteaching hospitals. There was more regionalization of liver, lung and esophageal operations versus breast and colon operations. CONCLUSIONS: Increased hospital procedure volume correlated with improved longterm survival for patients in Ontario who underwent some, but not all, cancer resections, whereas hospital teaching status had no significant impact on patient outcomes. Across the province, further regionalization of care may help improve the quality of some cancer procedures.     

Distribution of neuropeptide Y-like immunoreactivity in the brain of the lizard Gallotia galloti.

The distribution of neuropeptide Y (NPY)-like immunoreactivity was studied in the brain of the lizard Gallotia galloti, in order to gain insight into the comparative topography of this peptide. Antisera against both NPY and its C-terminal flanking peptide (C-PON) were used, demonstrating a general coexistence of both peptides, as described in other vertebrates. Most NPY-like immunoreactive (NPY-LI) cell bodies were observed in the telencephalon, specifically in various olfactory structures, all cortices, septum, basal ganglia (except for the globus pallidus), the nucleus of the diagonal band of Broca, the amygdaloid complex, and the bed nucleus of the anterior commissure. NPY-LI cells were also seen in the preoptic and hypothalamic regions and the dorsal thalamus (mainly in the perirotundal belt), as well as in the mesencephalic tegmentum (in the ventral tegmental area, the substantia nigra, and the retrorubral area). NPY-LI fibers and terminals were widely distributed in the brain. All visual and auditory neuropiles were densely innervated. Specially dense plexuses were seen in the nucleus accumbens, the ventral pallidum, the suprachiasmatic and ventromedial hypothalamic nuclei, the nucleus medialis thalami, the left habenula, and the central nucleus of the torus semicircularis. Our analysis shows that the distribution of NPY-like immunoreactivity in the forebrain of Gallotia largely resembles that of other vertebrates, whereas differences are mainly observed in the brainstem. The widespread distribution of NPY in the lizard brain suggests several modulatory functional roles, either in local-circuit systems of the forebrain, or in various limbic, neuroendocrine, and sensory pathways.     

Morphological damage induced by Escherichia coli lipopolysaccharide in cultured hepatocytes: localization and binding properties

Lipopolysaccharides (LPS) from Gram-negative bacteria are considered to be the responsible agents for the induction of endotoxic shock, affecting the liver as a target organ. In this study, the cell morphology and some biochemical properties of 24 h-culture-hepatocyte monolayers treated with Escherichia coli 0111:B4 lipopolysaccharide, were observed. Cell morphology was observed by scanning electron microscopy and immunofluorescence methods. LPS interaction induced an increase in rounded cells with diminished adhesion capacity. As biochemical parameters, albumin synthesis and 2-deoxyglucose uptake were measured. LPS decreased the hexose uptake in a dose-dependent manner. Binding of (14C)LPS to cultured hepatocytes showed that LPS binds to non-specific constituents of the membrane bilayer.     

Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data.

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.