Helical tomotherapy with concurrent capecitabine for the treatment of inoperable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Helical tomotherapy, an advanced intensity-modulated radiation therapy with integrated CT imaging, permits highly conformal irradiation with sparing of normal tissue. Capecitabine, a pro-drug of 5-FU that induces thymidine phosphorylase can achieve higher levels of intracellular 5-FU when administered concurrently with radiation. We evaluated the feasibility as well as the clinical outcome of concurrent administration of capecitabine with tomotherapy in patients with advanced pancreatic cancer.</p> <p>Methods</p> <p>Nineteen patients with advanced pancreatic cancer including primarily unresectable disease and recurrence after curative surgery were included in the study. Two planning target volumes (PTV) were entered: PTV1 is gross tumor volume; and PTV2, the volume of the draining lymph nodes. The total doses to target 1 and target 2 were 55 and 50 Gy, respectively. Capecitabine at 1600 mg/m²/day was administered on each day of irradiation.</p> <p>Results</p> <p>Twenty six measurable lesions were evaluated. Overall in-field response rate was 42.3%; partial responses were achieved in 53.3% of the pancreatic masses, 28.6% of distant metastatic lesions and 25.0% of regional lymph nodes. The median duration of follow-up after tomotherapy was 6.5 months. None of the lesions showed in-field progression. Treatment was well tolerated with only minor toxicities such as grade 1 nausea (one patient), grade 1 hand-foot syndrome (one patient) and grade 1/2 fatigue (three patients).</p> <p>Conclusions</p> <p>Helical tomotherapy with concurrent capecitabine is a feasible option without significant toxicities in patients with advanced pancreatic cancer. We achieved excellent conformal distribution of radiation doses and minimal treatment-related toxicities with promising target volume responses.</p

Effect of respiratory syncytial virus infection on regulated on activation, normal T-cells expressed and secreted production in a murine model of asthma

PurposeSynthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question.MethodsWe prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid.ResultsRANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-γsynthesis nor airway responsiveness in either control or D. farinae mice.ConclusionRSV infection did not induce more RANTES in a murine model of asthma than in control mice

Anti-Allergic Activity of a Platycodon Root Ethanol Extract

Platycodon grandiflorum (Campanulaceae) is used as traditional medicine in Asian countries. In Korean traditional medicine, Platycodon root has been widely used since ancient times as a traditional drug to treat cold, cough and asthma. However, its effects on bone marrow-derived mast cell (BMMC)-mediated allergy and inflammation mechanisms remain unknown. In this study, the biological effect of Platycodon root ethanol extract (PE) was evaluated in BMMC after induction of allergic mediators by phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187) stimulation. The effect of PE on the production of several allergic mediators, such as interleukin-6 (IL-6), prostaglandin D2 (PGD2), leukotriene C4 (LTC4), β-Hexosaminidase (β-Hex) and cyclooxygenase-2 (COX-2) protein, was investigated. The results demonstrate that PE inhibits PMA + A23187 induced production of IL-6, PGD2, LTC4, β-Hexosaminidase and COX-2 protein. Taken together, these results indicate that PE has the potential for use in the treatment of allergy

Atopy and House Dust Mite Sensitization as Risk Factors for Asthma in Children

Asthma is commonly described as an atopic disease in childhood, but some cases of this disorder do not fit this description. The aim of this study was to evaluate the frequency of atopy, asthma, and sensitization to house dust mites in children with allergic symptoms. This study was performed at the Severance Hospital of Yonsei University with patients who visited the allergy clinic for evaluation of nonspecific upper respiratory symptoms, typical symptoms of asthma, or a general health workup. The patients were divided into three age groups: 0-3 years (group 1), 4-7 years (group 2), and 8-12 years (group 3). Of the 1,244 children examined, 844 (67.8%) were atopic and 400 (32.2%) were non-atopic. The frequency of atopy and asthma increased with age. Asthma was diagnosed in the same proportion (64%) of atopic and non-atopic children. As risk factors for asthma symptoms, the positive values of house dust mite (HDM) sensitivity were significantly increased in groups 1, 2, and 3 to 53.5%, 68.9%, and 80.2%, respectively. A significant difference between the percentage of asthmatics sensitized to HDM and that of asthmatics not sensitized to HDM was found only in group 3. In conclusion, asthma is related to atopy with increasing age, and house dust mite sensitization seems to be an important determinant of asthma in older children in Korea

Mortality from lung cancer in workers exposed to sulfur dioxide in the pulp and paper industry.

Our objective in this study was to evaluate the mortality of workers exposed to sulfur dioxide in the pulp and paper industry. The cohort included 57,613 workers employed for at least 1 year in the pulp and paper industry in 12 countries. We assessed exposure to SO(2) at the level of mill and department, using industrial hygiene measurement data and information from company questionnaires; 40,704 workers were classified as exposed to SO(2). We conducted a standardized mortality ratio (SMR) analysis based on age-specific and calendar period-specific national mortality rates. We also conducted a Poisson regression analysis to determine the dose-response relations between SO(2) exposure and cancer mortality risks and to explore the effect of potential confounding factors. The SMR analysis showed a moderate deficit of all causes of death [SMR = 0.89; 95% confidence interval (CI), 0.87-0.96] among exposed workers. Lung cancer mortality was marginally increased among exposed workers (SMR = 1.08; 95% CI, 0.98-1.18). After adjustment for occupational coexposures, the lung cancer risk was increased compared with unexposed workers (rate ratio = 1.49; 95% CI, 1.14-1.96). There was a suggestion of a positive relationship between weighted cumulative SO(2) exposure and lung cancer mortality (p-value of test for linear trend = 0.009 among all exposed workers; p = 0.3 among workers with high exposure). Neither duration of exposure nor time since first exposure was associated with lung cancer mortality. Mortality from non-Hodgkin lymphoma and from leukemia was increased among workers with high SO(2) exposure; a dose-response relationship with cumulative SO(2) exposure was suggested for non-Hodgkin lymphoma. For the other causes of death, there was no evidence of increased mortality associated with exposure to SO(2). Although residual confounding may have occurred, our results suggest that occupational exposure to SO(2) in the pulp and paper industry may be associated with an increased risk of lung cancer

Exhaled Nitric Oxide is Associated with Allergic Inflammation in Children

Exhaled nitric oxide (eNO) has been proposed as a noninvasive marker of airway inflammation in asthma. In asthmatic patients, exhaled NO levels have been shown to relate with other markers of eosinophilic recruitment, which are detected in blood, sputum, bronchoalveolar lavage fluid and bronchial biopsy samples. The purpose of this study was to assess the possible relationship between eNO and allergic inflammation or sensitization in childhood asthma and allergic rhinitis. Subjects consisted of 118 asthmatic children, 79 patients with allergic rhinitis, and 74 controls. Their age ranged from 6 to 15 yr old. eNO level, peripheral blood eosinophil count, eosinophil cationic protein (ECP), serum total IgE level and specific IgE levels were measured. Methacholine challenge test and allergic skin prick test for common allergens were performed in all subjects. Atopic group (n = 206, 44.48 ± 30.45 ppb) had higher eNO values than non-atopic group (n = 65, 20.54 ± 16.57 ppb, P < 0.001). eNO level was significantly higher in patients with asthma (42.84 ± 31.92 ppb) and in those with allergic rhinitis (43.59 ± 29.84 ppb) than in healthy controls (27.01 ± 21.34 ppb, P < 0.001) but there was no difference between asthma and allergic rhinitis group. eNO also had significant positive correlations with Dermatophagoides pteronyssinus IgE level (r = 0.348, P < 0.001), Dermatophagoides farinae IgE level (r = 0.376, P < 0.001), and the number of positive allergens in skin prick test (r = 0.329, P = 0.001). eNO had significant positive correlations with peripheral blood eosinophil count (r = 0.356, P < 0.001), serum total IgE level (r = 0.221, P < 0.001), and ECP (r = 0.436, P < 0.001). This study reveals that eNO level is associated with allergic inflammation and the degree of allergic sensitization

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Sucrose preferentially promotes expression of OsWRKY7 and OsPR10a to enhance defense response to blast fungus in rice

Sucrose controls various developmental and metabolic processes in plants. It also functions as a signaling molecule in the synthesis of carbohydrates, storage proteins, and anthocyanins, as well as in floral induction and defense response. We found that sucrose preferentially induced OsWRKY7, whereas other sugars (such as mannitol, glucose, fructose, galactose, and maltose) did not have the same effect. A hexokinase inhibitor mannoheptulose did not block the effect of sucrose, which is consequently thought to function directly. MG132 inhibited sucrose induction, suggesting that a repressor upstream of OsWRKY7 is degraded by the 26S proteasome pathway. The 3-kb promoter sequence of OsWRKY7 was preferentially induced by sucrose in the luciferase system. Knockout mutants of OsWRKY7 were more sensitive to the rice blast fungus Magnaporthe oryzae, whereas the overexpression of OsWRKY7 enhanced the resistance, indicating that this gene is a positive regulator in the plant defense against this pathogen. The luciferase activity driven by the OsPR10a promoter was induced by OsWRKY7 and this transcription factor bound to the promoter region of OsPR10a, suggesting that OsWRKY7 directly controls the expression of OsPR10a. We conclude that sucrose promotes the transcript level of OsWRKY7, thereby increasing the expression of OsPR10a for the defense response in rice