Clinical significance of vascular endothelial growth factor and Delta-like ligand 4 in small pulmonary adenocarcinoma

Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The notch ligand Delta-like ligand 4 (DLL4) is induced by VEGF and acts as a negative regulator of tumor angiogenesis by reducing the numbers of non-productive sprouting vessels. Several reports have shown the prognostic role of VEGF expression in non-small cell lung cancer. However, the correlation between VEGF and DLL4 expression and their clinical significance in non-small cell lung cancer remains unclear. The aim of this study was to analyze the correlation between the expression of VEGF/DLL4 and the clinicopathological background. Fifty-eight patients with lung adenocarcinomas measuring less than 3 cm in diameter who underwent surgical resection at Kawasaki Medical School Hospital from 2008 to 2010 were enrolled in this study. The expressions of VEGF, DLL4, CD31, and Ki-67 were analyzed using immunohistochemical staining. The tumor cells were VEGF-positive in 44 patients (75.9%) and DLL4-positive in 41 patients (70.7%). No statistically significant association was observed between the patients\u27 characteristics and VEGF/DLL4 expression. A high VEGF expression level tended to be associated with a high DLL4 expression level (P = 0.050, r = 0.258). The mean Ki-67 index was significantly lower in the patients with high VEGF expression (9.5 vs. 18.2, P = 0.011), but no significant difference was observed when patients were compared according to their DLL4 expression levels (11.8 vs. 11.0, P = 0.804). The mean Ki-67 index was higher in the VEGF_ DLL4_ patients than in the VEGFhigh DLL4high patients by a marginally significant difference (20.1 vs. 10.9 P = 0.056). The 3-year recurrence-free survival rates of the VEGF_/DLL4_ and the VEGF_/DLL4_ patients were 83.3% and 35.7%, respectively. The prognosis of the VEGF_/DLL4_ patients was significantly better than that of the VEGF_/DLL4_ patients (P = 0.032). To investigate the significance of the difference in tumor proliferation and prognosis between the VEGF_/DLL4_ and the VEGF_/DLL4_ patients, we evaluated the morphologic effect of VEGF/DLL4 expression on the intratumoral capillaries by counting the number of capillaries and calculating the luminal area (μm^2). No significant differences were seen between either the VEGF or DLL4 expression levels and the mean number of intratumoral capillaries or the luminal area (μm^2). In conclusion, VEGF_/DLL4_ patients with small pulmonary adenocarcinoma had a significantly poorer prognosis, although no significant difference in a morphological evaluation of the capillaries was seen between VEGF_/DLL4_ and VEGF_/DLL4_ patients

Interaction Energy Analysis for Drug-Cyclodextrin Inclusion Complexes in Aqueous Solutions

It is vital to elucidate the role of asymmetric intermolecular interactions resulting from the stereospecific structures of molecules in order to understand the mechanisms of chemical and biochemical reactions such as enzyme-substrate reactions, antigen-antibody reactions, etc. In order to reveal the mechanism of the inclusion phenomenon for b-cyclodextrin (CD)-ampicillin complexes and b-CD-ibuprofen complexes, binding free energies were determined using molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) analysis. To clarify the details of the interaction energies of these complexes, pair interaction energy decomposition analysis (PIEDA) was carried out. The direction of inclusion of drugs into b-CD cavities was clarified on the basis of results obtained using the above-mentioned methods

Prevalence of asthma, rhinitis and eczema among 13–14-year-old schoolchildren in Tochigi, Japan

To analyze the prevalence and severity of asthma, rhinitis and eczema in children living in different countries, the International Study of Asthma and Allergies in Childhood (ISAAC) was developed. The ISAAC Phase One study evaluated approximately 720 000 children in 56 countries, including Japan. In late 1995 and early 1996, we administered the ISAAC questionnaire to 4466 schoolchildren aged 13–14 years of age in 24 schools in Utsunomiya City and Tochigi City (both in Tochigi Prefecture, Japan). With regard to asthma, the reported prevalence of wheezing in the preceding 12 months was 8.4%, of frequent wheezing attacks 0.6% and of wheezing with sleep disturbance 0.5%. The prevalence in the preceding 12 months of rhinitis was 42.1% and of rhinoconjunctivitis was 21.5%. Nasal symptoms were most frequent in April (19.9%) and least frequent in July (5.6%). The prevalence of atopic eczema in the prior 12 months was 9.6% and atopic eczema with sleep disturbance was 0.6%. All prevalence values were slightly increased in Utsunomiya City, the largest city in Tochigi Prefecture, in comparison with Tochigi City. In conclusion, in Japanese cities, 33.3% of children had some allergic symptoms and 2.4% of children reported severe allergic symptoms

Risk factors for asthma allergic diseases among 13-14-year-old schoolchildren in Japan

ABSTRACTBackgroundTo identify risk factors for childhood wheezing and allergies, a questionnaire regarding family histories and environmental factors was added to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase One questionnaire and the associations between current prevalence and risk factors were analyzed.MethodsQuestionnaires were completed by 4466 schoolchildren, who were 13–14 years of age, in Tochigi Prefecture. Children were divided into groups on the basis of risk factors and the severity of each allergic disease according to answers to the ISAAC questionnaire.ResultsIn analyses of family histories, the odds ratios (OR) of children who have a family history with no symptoms were significantly lower by risk factor-based analyses compared with those children with a family history of symptoms of wheezing (OR = 2.34-4.39), rhinitis (1.76-2.68) and eczema (2.54-7.81), and significant correlations were observed between severity and family history in all diseases by the Mantel test (P < 0.001). Although the OR of household smoking was not significant, heavier smoking in a household had an effect on severity and showed a significant correlation with severity in rhinitis (P < 0.05) and eczema (P < 0.01). Regarding road traffic, the percentage of children living in an area with heavy traffic showed a significant correlation with the severity of wheezing (P < 0.05) and no children with severe wheezing lived in areas with light traffic. In addition, the mean percentage of children with current wheezing between school locations was significantly higher in the city area (10.2 ± 0.7%) compared with that in the suburbs (6.6 ± 0.9%; P = 0.01) and industrial areas (6.6 ± 0.7%; P = 0.01).ConclusionsThese results suggest that the family histories may have potential effects on the severity of allergic diseases and that household smoking for rhinitis and eczema and heavy road traffic for asthma may be more important modifiable risk factors for severity in Japan