Soo Keol Lee

Forkhead box M1 expression in pulmonary squamous cell carcinoma: correlation with clinicopathologic features and its prognostic significance ☆

Forkhead box M1 (FoxM1) transcription factor has been shown to play important roles in regulating the expression of genes that are involved in cell proliferation, differentiation, and transformation by promoting both G(1)/S and G(2)/M transition. Although it has been reported that the FoxM1 signaling network is frequently deregulated with an up-regulated FoxM1 expression in human malignancies, the role of FoxM1 in lung cancer remains to be determined. We performed immunohistochemical detection of FoxM1 protein in 69 tissue samples from patients with primary pulmonary squamous cell carcinoma using a tissue microarray, and Western blotting was done to confirm the immunohistochemical observations. FoxM1 immunoreactivity was observed in 26 (37.7%) of the 69 squamous cell carcinoma cases. Analysis of the FoxM1 expression in 12 squamous cell carcinoma tissues and 2 normal lung tissues by Western blotting confirmed the immunohistochemical results. A FoxM1 expression was more frequently detected in the moderately or poorly differentiated squamous cell carcinomas than in the well-differentiated squamous cell carcinomas (P = .008). The tumors with a positive FoxM1 expression more frequently showed lymph node metastasis (P = .027) and an advanced American Joint Committee on Cancer stage (P = .049). The Kaplan-Meier survival curves demonstrated that patients with a positive FoxM1 expression had a significantly shorter survival time than those patients with a negative FoxM1 expression (P = .003). The multivariate analysis revealed that the FoxM1 expression was an independent poor prognostic factor (P = .018). A subset of pulmonary squamous cell carcinoma with a FoxM1 expression was associated with progressive pathologic features and an aggressive clinical course.

Predictors of the Severity and Serious Outcomes of Anaphylaxis in Korean Adults: A Multicenter Retrospective Case Study

Purpose Differences in definitions of the condition, relevant triggers, and the geographical locations of study centers, cause estimates of the prevalence of anaphylaxis to vary. Recent epidemiological data indicate that the incidence of anaphylaxis is rising. Methods To investigate the causes and clinical features of anaphylaxis in Korean adults, factors associated with the severity of the condition, and serious outcomes, a retrospective medical record review was performed on adult patients diagnosed with anaphylaxis between 2007 and 2011 in 15 University Hospitals of South Korea. Results A total of 1,806 cases (52% male, age 16-86 years) were reported. Cutaneous symptoms (84.0%), combined with respiratory (53.9%) and/or cardiovascular (55.4%) symptoms, were the most frequent presentations. Using a recognized grading system, 1,776 cases could be classified as either mild, 340; moderate, 690; or severe, 746. Although eliciting factors varied significantly by age, gender, and regional and seasonal factors, drugs (46.5%; including nonsteroidal anti-inflammatory drugs, antibiotics, and radiocontrast media) were the most common cause of anaphylaxis, followed by foods (24.2%), insect stings (16.4%), exercise (5.9%), and unknown etiology (7.0%). All of age, multi-organ involvement, a history of allergic disease, and drug-induced anaphylaxis, were significant predictors of serious outcomes requiring hospital admission or prolongation of hospital stay. Epinephrine auto-injectors were prescribed for 7.4% of reported cases. Conclusions The principal causes of anaphylaxis in Korean adults were drugs, food, and insect stings. Drug-associated anaphylaxis, a history of allergic disease, multi-organ involvement, and older age, were identified as predictors of serious outcomes.

Longitudinal study of specific antibodies to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate in patients with TDI-induced asthma

Background : An appreciable number of patients with toluene diisocyanate (TDI)-induced asthma have high serum levels of specific IgE (sIgE) antibody to TDI-human serum albumin conjugate (HSA). A recent investigation suggested a role of specific IgG (sIgG) in the development of TDI asthma. Methods : We observed the changes in the levels of specific IgE and IgG antibodies to TDIHSA conjugate in TDI-induced asthmatic patients during seven years avoidance. Results : Six subjects with high sIgE and five with high sIgG were enrolled. All of them had taken anti-asthmatic medications with complete avoidance. Serum levels of sIgE and sIgG to TDI-HSA conjugate were detected by ELISA. The level of sIgE continued to decline up to 7 years and the mean half-life was 3.9 years. The mean half-life of sIgG was 4.5 yrs. Conclusion : These findings suggest that both sIgE and sIgG to TDI-HSA conjugate may persist for several years after the last exposure to TDI.

Chestnut as a Food Allergen: Identification of Major Allergens

To evaluate the clinical significance of chestnut as a food allergen in Korea, skin prick test and ELISA were done in 1,738 patients with respiratory allergies. To identify the IgE binding components, IgE-immunoblotting, 2D IgE-immunoblotting and MALDI-TOF were performed. To observe the effects of digestive enzymes and a boiling treatment, simulated gastric fluid (SGF) and simulated intestinal fluids (SIF) were incubated with chestnut extracts, and IgE-immunoblotting were then repeated. Skin prick test revealed that 56 (3.2%) patients showed more than 2+ of allergen to histamine ratio to chestnut. Among the 21 IgE binding components, 9 bands were found in more than 50% of the sera tested and the 24 kDa protein had the highest binding intensity. The amino acid sequence of the 24 kDa protein (pI 6.3) had homology with legume protein of oak tree. SGF, SIF and boiling treatment were able to suppress the IgE binding components. In conclusion, chestnut ingestion was shown to induce IgE mediated responses with a 3.2% sensitization rate. Twenty one IgE binding components and one new allergen (the 24 kDa protein) were identified. Digestive enzymes and boiling treatment were able to decrease the allergenic potency.

Predictors of Asthma Control by Stepwise Treatment in Elderly Asthmatic Patients

The geriatric population is increasing, and asthma severity increases with age. We determined the predictors of asthma control, exacerbation, and the factors that affect asthma-specific quality of life (A-QOL) in elderly asthmatic patients. This was a prospective, multicenter, real-life study for 6 months with stepwise pharmacologic treatment based on the Global Initiative for Asthma (GINA) guideline. A total of 296 asthmatic patients aged ≥ 60 yr were recruited from 5 university centers in Korea. The improved-asthma control group was defined as the group of patients who maintained well-controlled or improved disease and the not-improved asthma control group was defined as the remaining patients. Fewer number of medications for comorbidities (2.8 ± 3.3 in the improved vs. 4.5 ± 4.4 in the control) and higher physical functioning (PF) scale (89.8 ± 14.2 in the improved vs. 82.0 ± 16.4 in the control) were significant predictors in the improved-asthma control group (OR = 0.863, P = 0.004 and OR = 1.028, P = 0.018, respectively). An asthma control test (ACT) score of ≤ 19 at baseline was a significant predictor of asthma exacerbation (OR = 3.938, P = 0.048). Asthma duration (F = 5.656, P = 0.018), ACT score (F = 12.237, P = 0.001) at baseline, and the presence of asthma exacerbation (F = 5.565, P = 0.019) were significant determinants of changes in A-QOL. The number of medications for comorbidities and performance status determined by the PF scale may be important parameters for assessing asthma control in elderly asthmatic patients. Graphical Abstract

Characteristics of additional primary malignancies in Korean patients with non-small cell lung cancer.

BACKGROUND Long-term cancer survival results in increasing numbers of multiple primary malignancies in one person, which represents growing clinical challenge in patients with lung cancer. This study was intended to assess the incidence rate, temporal relationship, and characteristics of additional primary malignancies (APM) in Korean patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS We reviewed all 632 NSCLCs (313 adenocarcinomas, 276 squamous cell carcinomas, and 43 other NSCLCs) patients who underwent curative resection of NSCLC at the Dong-A University Medical Center from January 1991 to December 2009. We used the hospital information system and medical record to collect data about these patients and their tumors. In the data base, the following parameters were recorded: patients demographics (age, gender and smoking habit), time interval between the diagnosis of the NSCLC and APM, NSCLC characteristics (date of diagnosis, histology, TNM staging, operative details, and survival) and characteristics of APM (site of tumor, date of diagnosis, histology, TNM staging, operative details, and survival). RESULTS Eighty-one (12.8%) of the 632 patients with NSCLC had APMs. Thirty-three patients (40.8%) had APM in their history [occurring earlier than six months or more before NSCLC diagnosis; prior (P) group], 18 patients (22.2%) were diagnosed with an APM synchronously [diagnosed within six months before or after NSCLC; synchronous (S) group], and the remaining 30 patients (37.0%) were diagnosed with an APM during the follow-up period [occurring six months or more after NSCLC diagnosis; metachronous (M) group]. The second primary malignancy occurred most often two to five years in both P group (39.4%) and M group (36.7%). The most frequent APM was stomach cancer (25.0%), followed by colorectal cancer (19.0%), and thyroid cancer (10.7%). Interestingly, we found difference in the incidence of APM between different NSCLC histotypes. In the adenocarcinoma group, colorectal cancer was the most frequently discovered [12 of 46 events (26.1%)], followed by thyroid cancer [9 of 46 events (19.6%)]. In the squamous cell carcinoma group, stomach cancer occurred most frequently [12 of 36 events (33.3%)]. CONCLUSIONS APMs are commonly seen in patients with NSCLC, either preceding or following its occurrence. Therefore, it is important to recognize the characteristic of NSCLC patients with APM in order to detect the second primary malignancy as early as possible and to achieve a possible cure of disease.

A Case of Sorafenib-induced DRESS Syndrome in Hepatocelluar Carcinoma

Sorafenib is currently the only targeted therapy available for advanced stage hepatocellular carcinoma (HCC). Cutaneous adverse events associated with sorafenib treatment include hand-foot skin reaction, but there has been no report of drug reaction (or rash) with eosinophilia and systemic symptoms (DRESS) syndrome. Here, we report a case of 72-year-old man with HCC and alcoholic liver cirrhosis who developed skin eruptions, fever, eosinophilia, and deteriorated hepatic and renal function under sorafenib treatment. He has since successfully recovered with conservative care.

Immunologic Evaluation of Patients with Cefotetan-Induced Anaphylaxis

Cefotetan is a commonly prescribed second-generation cephalosporin that acts against a wide range of bacteria. However, cefotetan-induced hypersensitivity has rarely been reported. We report 2 cases of cefotetan-induced anaphylaxis with immunologic evaluation. The first case was a 70-year-old asthmatic woman who had dyspnea and hypotension during administration of cefotetan, in which high serum-specific IgE to cefotetan-human serum albumin (HSA) conjugate was detected by enzyme-linked immunosorbent assay. The second case was a 63-year-old asthmatic woman who complained of chest tightness and dyspnea during cefotetan infusion, in which high serum-specific IgG1 and IgG4 with no serum specific IgE to cefotetan-HSA conjugate was detected. The basophil activation test using basophils from the patient showed a significant up-regulation of CD63 with the addition of anti-IgG4 antibody compared with that in non-atopic healthy controls. In conclusion, cefotetan can induce anaphylaxis, which may involve both IgE- and IgG4-mediated responses in the pathogenic mechanism.

Relationship between PTEN and Vascular Endothelial Growth Factor Expression in Non-Small Cell Lung Cancer.

PURPOSE This study was performed to determine the relationship between PTEN and vascular endothelial growth factor (VEGF) expression and to assess their roles in the tumor-induced angiogenesis and tumor progression in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Formalin-fixed, paraffin-embedded tissues, from 96 patients diagnosed with NSCLC, were evaluated for VEGF and PTEN expression using immunohistochemical methods. The results of the expression pattern of VEGF alone, or in combination with PTEN expression, were compared with clinicopathological parameters. RESULTS VEGF expression was seen in 54 (56.3%) of the 96 NSCLCs evaluated, and was significantly correlated with histological type, and seen more frequently in adenocarcinomas compared to the other histological types (p<0.05). There were no significant associations between VEGF expression and tumor size, lymph node metastasis and stage. The microvessel density (MVD) determined by CD34 staining were significantly higher in tumors with VEGF expression (62.9+/-21.8) than those without (55.1+/-15.1). Loss of PTEN expression was seen in 33 (34.4%) of the 96 NSCLCs evaluated. VEGF expression was more frequently detected in the tumors with loss of PTEN expression (69.7%) than in those with PTEN expression (49.2%). When the combined VEGF/ PTEN phenotypes were divide into two groups; group I (VEGF-/PTEN+) and group II (VEGF-/ PTEN-, VEGF+/PTEN+, VEGF+/PTEN-), a significant correlation was also seen between the groups and the histologic types. There was a trend for the tumors in group II to show more frequent lymph node metastasis (50.0%) than those in group I (31.5%), although there was no statistical significance. The MVDs were significantly higher in group II (63.1+/-20.7) than in group I (53.4+/-17.2). CONCLUSION These findings demonstrate an inverse correlation between the expressions of PTEN and VEGF. It is possible that PTEN may repress VEGF expression, and modulate VEGF-mediated angiogenesis, which suggests further analysis of the complex phenomenon of neo-angiogenesis in NSCLC is essential.

A Computerized Asthma-Specific Quality of Life: A Novel Tool for Reflecting Asthma Control and Predicting Exacerbation

Background: Proper assessment of health-related quality of life is essential to achieve and maintain a controlled status in asthmatic patients. We developed our own computerized asthma-specific quality-of-life (cA-QOL) questionnaire based on in-depth interviews with adult asthmatic patients. In this study, we evaluated this cA-QOL in terms of the Asthma Control Test (ACT) score and Global Initiative for Asthma (GINA) guidelines as well as asthma exacerbation, and compared it with the asthma-related quality-of-life questionnaire (AQLQ). Methods: We conducted a multicenter, prospective, observational study in 133 adult asthmatic patients recruited from 5 university hospitals in South Korea, who were randomized into 2 groups according to the operating order of the cA-QOL and AQLQ. At every visit (3-month interval), physicians evaluated asthma control status with monitoring spirometry. The self-administered cA-QOL, AQLQ(S) and ACT were completed. Results: The cA-QOL scores correlated significantly with ACT and AQLQ(S) scores (r = 0.814, p < 0.001; r = 0.900, p < 0.001). The cA-QOL score was significantly lower where the ACT score was <19, in the patients with an uncontrolled asthma status according to the GINA guidelines and in those with asthma exacerbation (p < 0.001, respectively). A multivariate analysis showed that this cA-QOL was a significant parameter associated with an uncontrolled asthma status and asthma exacerbation (p < 0.001, p = 0.045, p = 0.019, respectively). Conclusion: The cA-QOL is a valid tool for reflecting current asthma control status and for assessment to predict the future risk of asthma exacerbation in adult asthmatics.