Insulin receptor substrate-1 (IRS-1) is an adaptor protein for insulin-like growth factor (IGF) signaling and it is presumed associated with cancer development, progression or clinical outcome of patients harboring solid tumors. Therefore, we investigated by immunohistochemistry, the expression of IRS-1 in the tumor tissues from 94 patients who were diagnosed as stage I non-small cell lung cancer (NSCLC) and had undergone a curative lung resection. The relationships between its intratumoral expression and various clinical parameters were explored. IRS-1 is consistently expressed in the cytoplasm of intrapulmonary bronchial and bronchiolar epithelial cells comprising normal appearing adjacent lung tissues. Forty-one (43.6%) of 94 specimens showed loss of IRS-1 expression. In a subset analysis, IRS-1 was more frequently lost in stage IB than in IA tumors (50.0 vs. 22.7%, p=0.024, ¯2 test), which was reflected by the facts that tumors which showed down-regulation of IRS-1 had larger area than those with IRS-1 expression (18.1 vs. 12.1 cm 2 , p=0.044, t-test). Down-regulation of IRS-1 is more frequently observed in squamous cell carcinoma than other cell type lung cancer (p=0.002, ¯2 test) and its expression was not affected by histological grade of differentiation. Comparing pack-years (P.Y.) between groups of smokers whose tumor expressed IRS-1 and those that did not, smokers whose tumor showed loss of IRS-1 expression had higher P.Y. than those whose tumor did express IRS-1 (39.2±23.67 vs. 25.6±26.61 P.Y., p=0.034, t-test). Intratumoral expression of IRS-1 did not influence disease-free survival, disease-specific survival or overall survival of stage I NSCLC patients, whose median follow-up duration is 7.5 years (95% CI; 7.21-7.86 years). These results suggest that loss of IRS-1 might rather be an early event in NSCLC development than a prognostic factor and that it is more strongly related with squamous cell carcinoma and with smoking.

Abstract. B-cell lymphoma-extra large (Bcl-X l ) has been known to suppress serum deprivation-induced cell death, while reactive oxygen species modulator 1 (romo1) is responsible for a serum deprivation-induced increase in reactive oxygen species (ros). therefore, we investigated whether Bcl-X l expression could inhibit the serum deprivation-induced increase in ros and cell death, which are mediated by romo1. We found that Bcl-X l expression effectively blocked serum deprivation-and romo1-triggered ros generation. Bcl-X l also inhibited apoptotic cell death induced by both serum deprivation and oxidative stress. From these results, we suggest that increased Bcl-X l expression, which is observed in many cancer cells, confers resistance to oxidative stress in the cancer cells by suppressing romo1-mediated oxidative stress.

Baek-ok injection (glutathione) has been widely used antioxidant therapy to whiten and has antiaging effects in Korea. Glutathione is an enzyme which synthesizes leukotriene, then it can induce asthma attack theoretically; however, there have been few case reports concerning this therapy. In this report, we described a 41-year-old woman who developed glutathione-induced life-threatening asthma attack. She has asthma history controlled by an intermittent salbutamol inhaler. She developed general weakness and dyspnea right after glutathione injection, and injection was discontinued. Dyspnea was progressively aggravated, and she lost consciousness with shock. Cardiopulmonary resuscitation was started, and she arrived at the Emergency Department with wheezing, hypoxia, severe respiratory acidosis, and nonmeasurable blood pressure. Intubation and mechanical ventilation were started with intramuscular epinephrine/intravenous methylprednisolone injection and repeated salbutamol/ipratropium/budesonide inhalation. After 5 hours, extubation and spontaneous breathing were successful without wheezing. Next day, pulmonary function test showed moderate an obstructive airway disease pattern, and she was discharged with inhaled fluticasone/salmeterol, oral methylprednisolone, and montelukast. We can exclude anaphylaxis, because serum tryptase obtained at the Emergency Department was 0.0 mg/dL and the absence of skin lesions and angioedema at arrival. Baek-ok injection (glutathione) should be carefully performed in asthma patients.