Yutaka Nishigaki

Resistin Is Closely Related to Systemic Inflammation in Obstructive Sleep Apnea

Background: Obstructive sleep apnea (OSA) is closely related to systemic inflammation. Resistin is an adipocyte-derived cytokine (adipokine) that may link obesity with inflammation. Objective: We aimed to investigate whether incremental changes in OSA severity, from normal to severe, primarily affect the levels of resistin and other adipokines. Methods: Serum levels of resistin, interleukin-6 (IL-6) and leptin were examined in 31 men with OSA and 10 men without OSA, matched for age, body mass index (BMI) and several metabolic profiles. In 11 of the 31 men with OSA, these mediators were reexamined after 3 months of nasal continuous airway pressure (nCPAP) therapy. Results: Levels of resistin and IL-6 were simultaneously elevated in men with OSA compared with those in men without OSA (p < 0.05), while levels of leptin did not differ. The resistin and IL-6 levels tended to increase with increasing disease severity (p < 0.05), which was based on the apnea-hypopnea index (AHI). The average oxyhemoglobin saturation during sleep (p < 0.01) and IL-6 (p < 0.05) emerged as significant determinants of resistin, even after adjustments for age, BMI, leptin levels and metabolic risk factors. After nCPAP therapy, the elevated levels of resistin and IL-6 decreased, reaching almost baseline levels of controls. Before treatment, AHI correlated positively with the reduction rate in resistin (p < 0.05). Conclusion: In OSA patients, resistin production can be enhanced by hypoxic stress during sleep, possibly mediating systemic inflammatory processes. nCPAP therapy may play a beneficial role in the control of resistin production.

Expression of syndecan-1 is common in human lung cancers independent of expression of epidermal growth factor receptor

In order to determine syndecan-1 expression in lung cancer, we examined 115 lung cancer specimens and 17 lung cancer cell lines. Syndecan-1 was immunohistochemically stained with a polyclonal antibody in 115 paraffin-embedded specimens; 84 cases out of 97 non-small cell lung cancer (NSCLC) and eight cases out of 18 small cell lung cancer (SCLC) were positively stained. Simultaneously, epidermal growth-factor receptor (EGFR) was stained; 47 cases out of 97 NSCLC and one case of 18 SCLC were positively stained. No significant correlation was shown between EGFR and syndecan-1 expression (P=0.68). Syndecan-1 mRNA was detectable in 16 of 17 lung cancer cell lines and EGFR mRNA in nine of 17. Eight cell lines had syndecan-1 mRNA as well as EGFR mRNA. PR-39 (1 microM) and 80 pM transforming growth factor-beta(1) (TGF-beta(1)), did not increase expressions of syndecan-1 mRNA and EGFR in five lung cancer cell lines. We concluded that lung cancer had detectable syndecan-1; however, expression of syndecan-1 protein did not correlate with survival time of lung cancer patients.

Increased serum level of vascular endothelial growth factor in Mycobacterium avium complex infection.

Objective:  Pulmonary infection caused by Mycobacterium avium complex (MAC) is one of the granulomatous diseases which are associated with the expression of vascular endothelial growth factor (VEGF). The aim of the present study was to clarify the association of VEGF with the pathogenesis of MAC infection.

Detection of Photofrin Fluorescence From Malignant and Premalignant Lesions in the Bronchus using a Full-color Endoscopic Fluorescence Imaging System.

Study objectives: To detect invisible lung cancer and to determine field of laser radiation during PDT we developed a full-color fluorescence fiberscopic system. We tested the efficacy of this system in patients with various bronchial malignancies. System design: A fiber-optic endoscope was attached to a camera box containing a color ICCD camera which can detect from 400 to 700nm fluorescence in full-color. Light of average wavelength 405 nm was selected and radiated through the light channel of the fiberscope from a 300W Xenon lamp. Patients and methods: We examined nine consecutive patients with bronchial malignancy admitted in our hospital to receive PDT. Sixteen lesions in these nine patients were observed with white light and excitation light and the results were compared. Histological examinations were done by taking biopsy specimens and samples for pathological and cytological examination. After the diagnosis was confirmed, 2.0 mg/kg Photofrin was injected. Forty eight hours after the administration of Photofrin, observation of the bronchial wall was made using a full-color endoscopic fluorescence imaging system just before PDT. Results: Bright red fluorescence from Photofrin was Observed in 14/14 bronchial malignancies: 3 squamous cell carcinoma, 9 squamous cell carcinoma in situ, 1 metastatic breast cancer and 1 metastatic islet cell tumor. Bright red fluorescence was also detected in 2/2 squamous dysplasia. Green autofluorescence was observed in the normal part of the bronchus. Conclusions: Results of the present study suggest that the full-color endoscopic fluorescence imaging system can be used to detect malignant and premalignant lesions as red fluorescence against green autofluorescence with Photofrin administration, and this system has the potential to detect absence of autofluorescence in cancerous lesions.

Abstract 903: Long-term survivors in advanced non-small cell lung cancer

Background: It is known that chemotherapy for advanced non small-cell lung cancer (NSCLC) improves the prognosis, however, with regard to 2-year survival rate of inoperable stage III/IV patients is up to 20%. The contribution of chemotherapies for survival is not fully satisfied yet. Purpose: The aim of this study is to evaluate the rate of long-term survival of more than 2 years in patients with advanced NSCLC and elucidate clinical factors that affect long-term survival in those patients. Methods: We retrospectively reviewed 103 patients with inoperable, stage III/IV NSCLC treated with chemotherapy from January 2005 to December 2006 at Dohoku National Hospital. These included 69 adenocarcinomas, 22 squamous cell carcinomas, 9 large cell carcinomas and 3 others. These patients were divided into two groups: those who survived more than 2 years (long-term survivors; LTS) and the others (non long-term survivors; non LTS). We analyzed the prognostic factors that affect the survival in this setting. The difference of characteristics between two groups was tested with the Mann-Whitney U test, the chi-square test or Fisher9s exact test. Survival curves were calculated according to Kaplan-Meier method. The correlations of variables with survival were analyzed by multivariate analysis using a Cox proportional hazards model. Results: There were 27 (26.2%) patients who survived more than 2 years (LTS). All of them had performance status (PS) 0 or 1. These LTS included 13 females, 11 non-smoker, 21 adenocarcinomas and 17 stage IV disease. LTS showed significant correlation with gender, smoking status, intrapulmonary metastases, response of 1st-line chemotherapy (SD or better), and response of gefitinib (SD or better) (p=0.0008, p=0.0457, p=0.0317, p=0.0004 and p=0.0026, respectively). Patients who respond to initial chemotherapy (SD or better) as well as gefitinib showed favorable course. Univariate analyses showed that PS 0-1, intrapulmonary metastases, response of 1st-line chemotherapy (SD or better), response of gefitinib (SD or better) were significantly associated with better prognosis (p=0.0036, p=0.0203, p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 903.

Contents Vol. 76, 2008

I. Adcock, London H.D. Becker, Heidelberg D. Bouros, Athens N.S. Cherniack, Newark, N.J. K.F. Chung, London V. Cottin, Lyon C. Dooms, Leuven S. Gasparini, Ancona P.M. Gustafsson, Göteborg J. Hammer, Basel C. Kroegel, Jena F. Kummer, Vienna P.N. Mathur, Indianapolis, Ind. L.P. Nicod, Lausanne T. Nishino, Chiba M. Noppen, Brussels D. Olivieri, Parma C.P. Page, London E.W. Russi, Zürich J. Vansteenkiste, Leuven Editorial Board