Young June Jeon

Patient's Perception of Symptoms Related to Morning Activity in Chronic Obstructive Pulmonary Disease: The SYMBOL Study

Background/Aims Patients with chronic obstructive pulmonary disease (COPD) experience more problematic respiratory symptoms and have more trouble performing daily activities in the morning. The aim of this study was to assess the perception of COPD symptoms related to morning activities in patients with severe airflow limitation. Methods Data of 133 patients with severe airflow limitation were analyzed in a prospective, non-interventional study. A clinical symptom questionnaire was completed by patients at baseline. In patients having morning symptoms, defined by at least one or more prominent or aggravating symptom during morning activities, a morning activity questionnaire was also completed at baseline and following 2 months of COPD treatment. Results The most frequently reported COPD symptom was breathlessness (90.8%). Morning symptoms were reported in 76 (57%) patients; these had more frequent and severe clinical COPD symptoms. The most frequently reported morning activity was getting out of bed (82.9%). The long acting muscarinic antagonist (odds ratio [OR], 6.971; 95% confidence interval [CI], 1.317 to 11.905) and chest tightness (OR, 0.075; 95% CI, 0.011 to 0.518) were identified as significantly related to absence of morning symptoms. There was no significant correlation between the degree of forced expiratory volume in 1 second improvement and severity score differences of all items of morning activity after 2-month treatment. Conclusions Fifty-seven percent of COPD patients with severe airflow limitation have morning symptoms that limit their morning activities. These patients also have more prevalent and severe COPD symptoms. The results of this study therefore provide valuable information for the development of patient-reported outcomes in COPD.

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

BACKGROUND Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.BACKGROUND Biological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue. PATIENTS AND METHODS Expression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients. RESULTS Low expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. CONCLUSIONS The proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.

Paclitaxel-Loaded Polymeric Micelle (230 mg/m2) and Cisplatin (60 mg/m2) vs. Paclitaxel (175 mg/m2) and Cisplatin (60 mg/m2) in Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase IIB Trial

INTRODUCTION The development of paclitaxel-loaded polymeric micelle (PPM) has circumvented many of the infusion-related difficulties associated with standard solvent-based paclitaxel. PPM plus cisplatin combination chemotherapy showed significant antitumor activity in phase I and II studies. This prospective randomized controlled phase IIB study assessed the noninferiority of the efficacy and tolerability of high-dose PPM plus cisplatin to a standard dose of paclitaxel plus cisplatin. PATIENTS AND METHODS Patients with stage IIIB/IV or recurrent non-small-cell lung cancer (NSCLC) who were chemonaive were eligible for participation. The patients were randomly assigned to receive PPM 230 mg/m(2) plus cisplatin 60 mg/m(2) or paclitaxel 175 mg/m(2) plus cisplatin 60 mg/m(2) once every 3-week cycle. The primary endpoint was to compare the response rate (RR) between the groups with coprimary analyses to assess noninferiority. Secondary endpoints included progression-free survival, overall survival, and safety. RESULTS A total of 276 patients were randomized to PPM plus cisplatin (n = 140) or paclitaxel plus cisplatin (n = 136). RR was 43.6% in the PPM plus cisplatin group and 41.9% in the paclitaxel plus cisplatin group. Noninferiority of PPM plus cisplatin compared with paclitaxel plus cisplatin was confirmed for RR. There were no differences in progression-free survival and overall survival between the groups. Although there was a higher rate of grade 3 neutropenia in the PPM plus cisplatin group, the overall rate of adverse events was comparable between the 2 groups. CONCLUSION PPM in combination with cisplatin was well tolerated, and its response rate was noninferior to that of paclitaxel plus cisplatin in patients with advanced NSCLC and who were chemonaive.

Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE).

Background This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patients characteristics of modified intent-to-treat population. Results A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

Prevalence, risk factors and survival of lung cancer in the idiopathic pulmonary fibrosis

Background:  The aim of this study was to evaluate the prevalence, risk factors, and survival of lung cancer in patients with idiopathic pulmonary fibrosis (IPF).

Abstract 4659: Phase II study of a weekly liposomal paclitaxel formulation (Genexol®-PM) and gemcitabine® combination chemotherapy in patients with advanced biliary cancer.

OBJECTIVE: Advanced biliary cancer is associated with a poor prognosis due to wide resistance to chemotherapeutic agents. This phase II clinical trial was conducted to determine the efficacy and safety of weekly gemcitabine and liposomal paclitaxel in patients with unresectable of metastatic biliary cancer. METHODS: The eligibility criteria were patients 1) with pathologically proven biliary cancer, 2) with an ECOG performance status 0 to 2, 3) aged more than 18, 4) with measurable lesions, 5) with adequate hematologic, renal and liver functions, and 6) who provided written informed consent. Each treatment cycle was consisted of gemcitabine 1000 mg/m² and liposomal paclitaxel (Genexol-PM)100 mg/m² on days 1, 8 followed by rest perioid of 14 days. It was repeated until the appearance of disease progression or unacceptable toxicity up to maximal 10 cycles. The primary end point of this study was reponse rate, and secondary end points included toxicity, progression free survival and overall survival. RESULTS: Forty five patients were enrolled; median age was 63 years; male (n=33) and female (n=12). The median number of cycles administered was 4.0 (range,1-10). Thirty nine patients were assessable for efficacy. Ten partial responses and 18 stable diseases were confirmed. Giving an overall response rate was 25.6% and disease control rate was 71.8% in per-protocol population. The median time to progression and median overall survival was 4.0 (95% CI; 3.17∼4.83) months and 8.13 (95% CI; 4.76∼11.51) months, respectively. MUC4 expression was not significantly correlated with overall survival and progression free survival (p=0.391). CONCLUSION: Weekly gemcitabine combined with Genexol-PM® appears to be effective against advanced biliary cancers. Further randomized trials are needed to confirm this finding. Citation Format: Keon Uk Keon Uk, Jin Young Kim, Young Rok Do, Hong Suk Song, Young June Jeon, Hun Mo Ryoo, Sung Hwa Bae, Jong Gwang Kim, Jin Ho Baek, Yee Soo Chae, Min Kyoung Kim, Kyung Hee Lee, Yoon Young Cho. Phase II study of a weekly liposomal paclitaxel formulation (Genexol®-PM) and gemcitabine® combination chemotherapy in patients with advanced biliary cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4659. doi:10.1158/1538-7445.AM2013-4659

Abstract 1865: Ciglitazone increases ovarian cancer cell death by inhibiting GLUT-1 expression.

Ciglitazone is a kind of thiazolidinedione and a potent, selective peroxisome proliferator-activated receptor γ (PPAR γ) ligand and it is active in vivo as an anti-hyperglycemic agent in the murine model. Glucose metabolism plays a key role in the maintenance of energy homeostasis in organisms and changes in cellular glucose uptake rate are found in malignant diseases. Significant increase in glucose consumption can be found in many malignant conditions and research so far has focused on its apoptotic and inhibition of proliferation properties but their role in cell death is unclear. We show that ciglitazone inhibits glucose uptake in ovarian cancer cell through GLUT-1 expression. In this study, we investigated the effect of ciglitazone to GLUT-1 expression and cell proliferation. We further demonstrate that ciglitazone pretreated tumor cell was increased apoptosis dose dependent manner and siGLUT-1 treated tumor cell showed increased apoptosis. Interestingly, not only cancer cell line but also in vivo state, ciglitazone could decrease tumor mass. Specificity protein (Sp) is highly expressed in tissues of prostate cancer, breast carcinomas and lung cancer when compared to normal tissues or cells. Previous studies showed that Sp1 plays an important role in carcinogenesis and metastasis of several human tumor types by regulating growth-related signal transduction, cell cycle control molecules, apoptosis, oncogenes, tumor suppressor genes. In this study there was no relation with apoptosis and SP1 expression. We demonstreated that ciglitazone inhibit glucose uptake in ovarian cancer cell lines and the relationship between ciglitazone and GLUT-1 in ciglitazone induced cell death. Citation Format: Jin Young Kim, So Jin Shin, Keon Uk Park, Young June Jeon, Chi Heum Cho, Eunyoung Ha. Ciglitazone increases ovarian cancer cell death by inhibiting GLUT-1 expression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1865. doi:10.1158/1538-7445.AM2013-1865

Abstract 4003: MicroRNA 99b down-regulation in lung cancer tissues leads to fibroblast growth factor receptor 3 up-expression and acceleration of proliferation

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Background: Dysregulation of miRNA expression has been identified in a number of cancers and an accumulating data indicate that some miRNAs can function as tumor suppressors or oncogenes and are important in cancer development. Deletion or loss of function of a tumor-suppressing miRNA results in overexpression of target oncogenes. Conversely, activation or overexpression of an oncogenic miRNA results in silencing of tumor-suppressing target genes. According to miRNA profiles on microarray, miR-99b was down-expressed in Korean lung cancer. FGFR-3 is predicted target of miR-99b through two public algorithms. FGFR-3 has been demonstrated to be involved in the RAS/RAF/MEK/MAPK pathway through activation of p90 ribosomal S6 kinase. It has been reported that FGFRs are frequently overexpressed in NSCLC cell lines, suggesting that an FGFR-dependent autocrine signaling pathway may operate in a subset of NSCLCs. Material & method: We studied expression of miR-99b and FGFR-3 using quantitative reverse transcription PCR (qRT-PCR) in lung cancer tissue. To examine whether miR-99b could regulate FGFR-3 in lung cancer, we performed transient transfection of pre-miR-99b into lung cancer cell line, then we performed qRT-PCR and western blot in HCC1438, HCC95, and H522 cells for analysis of FGFR-3 expression. We hypothesized the miR-99b has a role of inhibitor cell growth in lung cancer. To test this hypothesis, we performed cell proliferation assay. Results: miR-99b was down-regulated and FGFR-3 was up-regulated in lung cancer. Over-expression of miR-99b induced marked reduction of FGFR-3 mRNA levels and protein level in lung cancer cell line HCC1438, HCC95, and H522. The growth rate in miR-99b precursor treated cell was lower than in negative control of miR treated cell. Conclusion: Abnormal down-regulation of miR-99b could lead to the over-expression of FGFR-3 in lung cancer. miR-99b may be a potent tumor suppressor and may be a potential candidate of therapeutic tool in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4003. doi:10.1158/1538-7445.AM2011-4003

Prognostic Significance of Supraclavicular Lymph Nodes and Pleural Effusion In Small Cell Lung Cancer

Backgrounds : In the absence of distant metastasis, small cell lung cancer (SCLC) patients presenting with supraclavicular lymph node (SCLN) involvement and pleural effusion can benefit from thoracic radiotherapy. But there are some debate as to the prognostic significance of both SCLN involvement and pleural effusion. The purpose of this study was to determine the prognostic significance of SCLN involvement and pleural effusion in SCLC. Methods : Two Hundred and fifteen patients with histologically confirmed small cell lung cancer, who were treated either at the Keimyung university Dongsan hospital and Kyungpook national university hospital from January 1994 to June 1998, were evaluated retrospectively. The patients were classified as having either limited or extensive stage using the Veterans Administration staging system. Results : SCLN was presented in 10.5% of patients(n=21). The median survival was 247 days for patients with SCLN(n=21) and 264 days for patients without(n=194) (p=0.52). After treatment, the median survival was 298 days for patients with SCLN(n=13) and 348 days for patients without(n=115) (p=0.52). SCLN involvement was not correlated with the presence of distant metastases. Median survival was 459 days for patients with a limited stage without SCLN(n=66), 650 days for those with a limited stage with SCLN (n=7) (p=0.96). Pleural effusion was presented in 24.7% of patients(n=52). The median survival was 198 days for patients with pleural effusion(n=52) and 275 days for patients without(n=163) (p

A Case of Churg-Strauss Syndrome with Bilateral Pleural Effusions

A 26-year-old man with a one-year history of asthma and sinusitis presented with bilateral pleural effusions, patch basilar infiltrates on a chest x-ray and a pericardial effusion on an echocardiogram. The peripheral blood showed marked eosinophilia. An obstructive pattern was also observed during the pulmonary fuction test, which was responsive to bronchodilator inhalation. Nerve conduction studies showed right sural neuropathy. Thoracentesis yielded an acidotic exudative effusion with low glucose, low and eosinophilia. An open lung biopsy revealed an eosinophilic interstitial pneumonitis associated with a necrotizing eosinophilic vasculitis, and granulomatous inflammation foci. In the literature, pleural effusions were reported in 29 percent of Churg-Strauss patients, but the number of effusions was low and their characteristics have not been well described. This report describes the characteristic findings of pleural fluid and its histologic features in a case of classical Churg-Strauss syndrome.