Production of interleukin-10 by alveolar macrophages from lung cancer patients

AbstractInterleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean ± sem; 288·0 ± 56·7 vs. 249·6 ± 58·4 pg ml−1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152·3 ± 51·9 to 278·0 ± 112·8 pg ml−1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung

Lysophospahatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2

Division of Medical Oncology and Surgical Oncolog

Neighborhood built environment and physical activity of Japanese older adults: results from the Aichi Gerontological Evaluation Study (AGES)

<p>Abstract</p> <p>Background</p> <p>Although many studies have reported the association between neighborhood built environment (BE) and physical activity (PA), less is known about the associations for older populations or in countries besides the US and Australia. The aim of this paper is to examine the associations for older adult populations in Japan.</p> <p>Methods</p> <p>Our analyses were based on cross-sectional data from the Aichi Gerontological Evaluation Study (AGES), conducted in 2003. The respondents were older adults, aged 65 years or over (n = 9,414), from 8 municipalities across urban, suburban, and rural areas. The frequency of leisure time sports activity and total walking time were used as the outcome variables. Using geographic information systems (GIS), we measured residential density, street connectivity, number of local destinations, access to recreational spaces, and land slope of the respondents' neighborhoods, based on network distances with multiple radii (250 m, 500 m, 1,000 m). An ordinal logistic regression model was used to analyze the association between PA and BE measures.</p> <p>Results</p> <p>Population density and presence of parks or green spaces had positive associations with the frequency of sports activity, regardless of the selected buffer zone. The analysis of total walking time, however, showed only a few associations.</p> <p>Conclusions</p> <p>Our findings provide mixed support for the association between PA and the characteristics of BE measures, previously used in Western settings. Some characteristics of the neighborhood built environment may facilitate leisure time sports activity, but not increase the total walking time for Japanese older adults.</p

Follistatin suppresses the production of experimental multiple-organ metastasis by small cell lung cancer cells in natural killer cell-depleted SCID mice

Division of Medical Oncology and Surgical Oncolog

Intensification therapy with anti-parathyroid hormone-related protein antibody plus zoledronic acid for bone metastases of small cell lung cancer cells in severe combined immunodeficient mice

Division of Medical Oncology and Surgical Oncolog

Novel dual targeting strategy with vandetanib induces tumor cell apoptosis and inhibits angiogenesis in malignant pleural mesothelioma cells expressing RET oncogenic rearrangement

Division of Medical Oncology and Surgical Oncolog

Safety of Postoperative Administration of Human Urinary Trypsin Inhibitor in Lung Cancer Patients with Idiopathic Pulmonary Fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic glycoprotein which may potentially inhibit various inflammatory factors associated with the development and progression of IPF. The present study was done to evaluate the effects of administration of high dose ulinastatin in lung cancer patients with IPF immediately following lung resection.Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed resectable lung cancers, were eligible for the study. The effects of escalating doses of ulinastatin 3×10(5), 6×10(5), and 9×10(5) units/body/day, administered postoperatively for 3 days were evaluated. The endpoints were safety and feasibility.Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions potentially attributable to ulinastatin administration were observed. AE was seen in one patient at 3 months after surgery, but since this occurred shortly after administration of chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.Ulinastatin administration after lung resection in lung cancer patients with IPF was considered to be safe and feasible. Further study is planned at the highest dose of this study to evaluate efficacy.UMIN.ac.jp/ctr/UMIN000002410

Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations

Division of Medical Oncology and Surgical Oncolog

Assessing the association between all-cause mortality and multiple aspects of individual social capital among the older Japanese

<p>Abstract</p> <p>Background</p> <p>Few prospective cohort studies have assessed the association between social capital and mortality. The studies were conducted only in Western countries and did not use the same social capital indicators. The present prospective cohort study aimed to examine the relationships between various forms of individual social capital and all-cause mortality in Japan.</p> <p>Methods</p> <p>Self-administered questionnaires were mailed to subjects in the Aichi Gerontological Evaluation Study (AGES) Project in 2003. Mortality data from 2003 to 2008 were analyzed for 14,668 respondents. Both cognitive and structural components of individual social capital were collected: 8 for cognitive social capital (trust, 3; social support, 3; reciprocity, 2) and 9 for structural social capital (social network). Cox proportional hazard models stratified by sex with multiple imputation were used. Age, body mass index, self-rated health, current illness, smoking history, alcohol consumption, exercise, equivalent income and education were used as covariates.</p> <p>Results</p> <p>During 27,571 person-years of follow-up for men and 29,561 person-years of follow-up for women, 790 deaths in men and 424 in women were observed. In the univariate analyses for men, lower social capital was significantly related to higher mortality in one general trust variable, all generalised reciprocity variables and four social network variables. For women, lower social capital was significantly related to higher mortality in all generalised reciprocity and four social network variables. After adjusting for covariates, lower friendship network was significantly associated with higher all-cause mortality among men (meet friends rarely; HR = 1.30, 95%CI = 1.10-1.53) and women (having no friends; HR = 1.81, 95%CI = 1.02-3.23). Among women, lower general trust was significantly related to lower mortality (most people cannot be trusted; HR = 0.65, 95%CI = 0.45-0.96).</p> <p>Conclusions</p> <p>Friendship network was a good predictor for all-cause mortality among older Japanese. In contrast, mistrust was associated with lower mortality among women. Studies with social capital indices considering different culture backgrounds are needed.</p