1.Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.
Jae Cheol LEE ; Seung Hun JANG ; Kye Young LEE ; Young Chul KIM
Cancer Research and Treatment 2013;45(2):79-85
Since the first description of non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation as a distinct clinical entity, studies have proved EGFR tyrosine kinase inhibitors (TKIs) as a first choice of treatment. The median response duration of TKIs as a first-line treatment for EGFR mutant tumors ranges from 11 to 14 months. However, acquired resistance to EGFR-TKIs is inevitable due to various mechanisms, such as T790M, c-Met amplification, activation of alternative pathways (IGF-1, HGF, PI3CA, AXL), transformation to mesenchymal cell or small cell features, and tumor heterogeneity. Until development of a successful treatment strategy to overcome such acquired resistance, few options are currently available. Here we provide a summary of the therapeutic options after failure of first line EGFR-TKI treatment for NSCLC.
Carcinoma, Non-Small-Cell Lung
;
Drug Resistance
;
Epidermal Growth Factor
;
Lung
;
Population Characteristics
;
Protein-Tyrosine Kinases
;
Receptor, Epidermal Growth Factor
2.Molds Isolated from Pet Dogs.
Kye Seung JANG ; Yeo Hong YUN ; Hun Dal YOO ; Seong Hwan KIM
Mycobiology 2007;35(2):100-102
Pet dogs have been considered to be involved in the contamination of indoor air by serving as a source of providing molds at houses. Currently, information on the molds originated from pet dogs is rarely available in Korea. The present study was carried out to obtain basic information on the fungi present on pet dogs. For this, fungal isolation was performed to the skin and hairs of 70 pet dogs at different houses and veterinary hospitals. A total of 44 fungal isolates were obtained from skin (27 isolates) and hairs (17 isolates) of the dogs investigated. Based on the observation of microstructures and colony morphology, and the ITS rDNA sequence analysis, the fungal isolates were identified at the level of genus. The identified isolates belong to the genera of Alternaria, Aspergillus, Beauveria, Chrysosporium, Cladosporium, Penicillium, Scopulariopsis, and Trichoderma. Among these genera, Aspergillus (25%), Cladosporium (23%) and Penicillium (20.5%) were 3 major genera. 63% of the 44 isolates showed color changes on dermatophyte test medium (DTM). When we tested the growth ability of 44 isolates at 37degrees C, 45% of the isolates were able to grow. These results show that pet dogs could carry fungi having a potentiality of affecting on human health.
Alternaria
;
Animals
;
Arthrodermataceae
;
Aspergillus
;
Beauveria
;
Chrysosporium
;
Cladosporium
;
DNA, Ribosomal
;
Dogs*
;
Fungi*
;
Hair
;
Hospitals, Animal
;
Humans
;
Korea
;
Penicillium
;
Scopulariopsis
;
Sequence Analysis
;
Skin
;
Trichoderma
3.High Dose Ramipril Inhibits Connective Tissue Growth Factor Expression and Fibrosis in Type 2 Diabetic Rat Heart.
Kyoung Ho CHOI ; Sang Hong BAEK ; Won Jae LEE ; Kye Nam PARK ; Pum Joon KIM ; Ki Bae SEUNG ; Jang Seong CHAE ; Jae Hyung KIM ; Kyu Bo CHOI
Korean Circulation Journal 2006;36(9):635-643
BACKGROUND AND OBJECTIVES: Connective tissue growth factor (CTGF) is a profibrotic cytokine, which may play an important role in the development of diabetic cardiovascular complications. ACE inhibition significantly prevents cardiovascular events in diabetics, although the mechanism remains obscure. The purpose of this study was to explore the effect of ACE inhibitors on the expression of CTGF and oxidative stress in the diabetic heart, and determine the effects of long term treatment with ACE inhibitors on diabetic cardiomyopathy. MATERIALS AND METHODS: Thirty OLETF (Otsuka Long Evans Tokushima Fatty) diabetic and thirty LETO (Long Evans Tokushima Otsuka) nondiabetic control rats were randomized into four groups for 24 weeks of treatment with either ramipril (5 mg/kg/day, n=15, each groups) or saline (n=15, each groups). RESULTS: The OLETF diabetic rats had prominent perivascular fibrosis, as shown by picrosirius red stains, compared to the LETO nondiabetic rats. ACE inhibition significantly prevented perivascular fibrosis in OLETF rats (p<0.01). Immunohistochemical stains were used to detect proteins for the receptors of advanced glycation end products (RAGE), CTGF, collagen III and nitrotyrosine. Although there were no significant differences in the myocardiac collagen contents, as found by measuring the hydroxyproline concentration among the four groups, the OLFTF diabetic rats had significantly increased cardiac CTGF and collagen III protein expression compared with the nondiabetic rats. The ACE inhibitor attenuated the increases in RAGE (-50.3%; p<0.01), CTGF (-37.5%; p<0.01) and collagen III (-52.3%; p<0.01) expression in the diabetic heart microvascular area. The OLFTF rats showed marked an increment in cardiac nitrotyrosine, a marker of protein oxidation. Ramipril also inhibited the expression of cardiac nitrotyrosine (-78.3%; p<0.01). CONCLUSION: The present study shows a possible role of RAGE/nitrotyrosine/CTGF in the diabetic cardiomyopathy of OLETF rats. The long term treatment of high dose ACE inhibitors may have beneficial effects on the diabetic heart through both antioxidant and antifibrotic mechanisms.
Angiotensin-Converting Enzyme Inhibitors
;
Animals
;
Collagen
;
Coloring Agents
;
Connective Tissue Growth Factor*
;
Connective Tissue*
;
Diabetic Cardiomyopathies
;
Fibrosis*
;
Glycosylation End Products, Advanced
;
Heart*
;
Hydroxyproline
;
Oxidative Stress
;
Rage
;
Ramipril*
;
Rats*
;
Rats, Inbred OLETF
4.Metastatic involvement of the stomach secondary to lung carcinoma.
Hyun Soo KIM ; Woo Ick JANG ; Hee Seung HONG ; Chong In LEE ; Dong Ki LEE ; Suk Joong YONG ; Kye Chul SHIN ; Young Hak SHIM
Journal of Korean Medical Science 1993;8(1):24-29
Blood-borne metastatic involvement of the stomach by cancer is a rare entity. According to the number of reports in the literature, the most common tumors that spread to the stomach through the blood stream are malignant melanoma, breast carcinoma and lung carcinoma. Recently, two cases of metastatic involvement of the stomach secondary to lung carcinoma were diagnosed by gastroscopy. The first patient was a 66-year-old man who had primary lung carcinoma with multiple bone and subcutaneous metastases. Gastroscopy showed multiple submucosal tumors with central umbilications in the fundus and in the upper body of the stomach. Pathologic examination revealed massive submucosal infiltration and conical shaped and scanty deep mucosal infiltration of undifferentiated small cell carcinoma suggestive of metastatic involvement. The second patient was a 68-year-old man who had primary lung carcinoma with brain metastasis. Gastroscopy showed a large fungating mass in the greater curvature side of the stomach. Pathologic examination revealed poorly differentiated squamous cell carcinoma. We report the two cases of metastatic gastric cancer from lung carcinoma with the literature review.
Aged
;
Carcinoma, Small Cell/*secondary
;
Carcinoma, Squamous Cell/*secondary
;
Humans
;
Lung Neoplasms/*pathology
;
Male
;
Stomach Neoplasms/*secondary
5.Hepatic veno-occlusive disease may develop in secondary iron overloaded mice after allogeneic hematopoietic stem cell transplantation with total body irradiation.
Mi Young YEOM ; Yoo Jin KIM ; Nack Gyun CHUNG ; Jae Wook LEE ; Pil Sang JANG ; Bin CHO ; Chul Seung KYE ; Dae Chul JEONG
Blood Research 2015;50(3):140-146
BACKGROUND: The outcome of hematopoietic stem cell transplantation (HSCT) is poor in patients with secondary iron overload (SIO). We evaluated the relationship between SIO and veno-occlusive disease (VOD) in an animal model with radiation for HSCT. METHODS: We used a 6-week-old female BDF1 (H-2b/d) and a male C57/BL6 (H-2b) as recipient and donor, respectively. Recipient mice were injected intraperitoneally with 10 mg of iron dextran (cumulative doses of 50 mg, 100 mg, and 200 mg). All mice received total body irradiation for HSCT. We obtained peripheral blood for alanine transaminase (ALT) and liver for pathologic findings, lipid hyperoxide (LH) as reactive oxygen species (ROS), and liver iron content (LIC) on post-HSCT day 1 and day 7. The VOD score was assessed by pathologic findings. RESULTS: ALT levels increased depending on cumulative iron dose, with significant differences between days 1 and 7 for mice loaded with 200 mg of iron (P<0.01). LH levels significantly increased in mice loaded with 200 mg of iron compared to those in other groups (P<0.01). For mice loaded with 100 mg of iron, the LH level depended on the radiation dose (P<0.01). There was a statistically significant relationship among ALT, LH, and LIC parameters (P<0.05). Pathologic scores for VOD correlated with LIC (P<0.01). CONCLUSION: Livers with SIO showed high ROS levels depending on cumulative iron dose, and correlations with elevated liver enzyme and LIC. The pathologic score for VOD was associated with the LIC. Our results suggest that SIO may induce VOD after HSCT with irradiation.
Alanine Transaminase
;
Animals
;
Dextrans
;
Female
;
Hematopoietic Stem Cell Transplantation*
;
Hematopoietic Stem Cells*
;
Hepatic Veno-Occlusive Disease*
;
Humans
;
Iron Overload*
;
Iron*
;
Liver
;
Male
;
Mice*
;
Models, Animal
;
Reactive Oxygen Species
;
Tissue Donors
;
Whole-Body Irradiation
6.A Case of Pancreatic Arteriovenous Malformation Presenting Upper Gastrointestinal Bleeding.
Su Hee PARK ; Mi Jeong KIM ; You Sang KO ; You Jin LIM ; Seung Yong HAN ; Hyun Woo BYUN ; Min Ho CHOI ; Hyun Joo JANG ; Sea Hyub KYE ; Jin LEE
Korean Journal of Gastrointestinal Endoscopy 2007;35(5):359-363
A pancreatic arteriovenous malformation (AVM) is a very rare disease entity that is usually asymptomatic; however, it may present with a massive gastrointestinal hemorrhage. Recent advances in cross-sectional imaging and the widespread availability of angiography have contributed to the diagnosis of this condition. A patient was transferred to our clinic due to unknown origin gastrointestinal bleeding and upper abdominal pain. Double balloon enteroscopy and duodenoscopy revealed a bleeding pancreatico-cholangio-duodenal fistula. We were able to diagnose an arteriovnous malformation with a pancreatico-cholangio-duodenal fistula by the use of angiography and from the post-operative pathological findings.
Abdominal Pain
;
Angiography
;
Arteriovenous Malformations*
;
Diagnosis
;
Double-Balloon Enteroscopy
;
Duodenoscopy
;
Fistula
;
Gastrointestinal Hemorrhage
;
Hemorrhage*
;
Humans
;
Pancreas
;
Rare Diseases
7.A Clinical Consideration of Abdominal Aortic Aneurysm Rupture.
Seung Taek LIM ; Young Kyun KIM ; Jeong Kye HWANG ; Sang Dong KIM ; Sun Chul PARK ; Yong Sung WON ; Jang Sang PARK ; Ji Il KIM ; Sang Seob YUN ; In Sung MOON
Journal of the Korean Society for Vascular Surgery 2011;27(3):103-107
PURPOSE: With current advances in surgical technique, the prognosis for elective open repair of abdominal aortic aneurysm (AAA) has improved, but the mortality rate for ruptured AAA remains high. The aim of this study was to define the risk factors of AAA rupture. METHODS: We performed a retrospective analysis of 169 AAA patients who underwent open surgical repair between March 2000 and October 2010. According to the rupture, the patients were divided into 2 groups: 'ruptured' (n=41), 'non-ruptured' (n=128). To define the risk factor of ruptured AAA, we compared following variables between the 2 groups: clinical co-morbidities (hypertension, diabetes mellitus, ischemic heart disease, malignancies), diameter (maximal diameter of AAA), location of rupture, gender, and previous abdominal surgery history. RESULTS: Mean patient-age was 68.4+/-4.4 years (range: 32 to 86 years); the majority of patients were males, 135 (79.8%). Mean diameter of AAA was 6.67+/-2.0 cm (range: 4 to 15 cm); 'non-ruptured': 6.3+/-1.6 cm, 'ruptured': 7.8+/-2.6 cm. The risk of AAA rupture was statistically significantly increased with increased diameter of the AAA (P=0.007). On multivariateanalysis, the only statistically significant risk factor for AAA rupture was diameter of AAA (P=0.004). CONCLUSION: The only significant risk factor for AAA rupture found in this study is the diameter of AAA. To minimize the rupture rate of the AAA patients, we will have to closely monitor the size of AAA diameter.
Aortic Aneurysm, Abdominal
;
Diabetes Mellitus
;
Humans
;
Male
;
Myocardial Ischemia
;
Organothiophosphorus Compounds
;
Prognosis
;
Retrospective Studies
;
Risk Factors
;
Rupture
8.Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study
Taeyun KIM ; Tae Won JANG ; Chang Min CHOI ; Mi-Hyun KIM ; Sung Yong LEE ; Yoon Soo CHANG ; Kye Young LEE ; Seung Joon KIM ; Sei Hoon YANG ; Jeong Seon RYU ; Jeong Eun LEE ; Shin Yup LEE ; Chan Kwon PARK ; Sang Hoon LEE ; Seung Hun JANG ; Seong Hoon YOON ; Hyung-Joo OH
Cancer Research and Treatment 2023;55(4):1152-1170
Purpose:
This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group).
Materials and Methods:
In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes.
Results:
The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5).
Conclusion
This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.
9.Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer
Jang Ho LEE ; Eun Young KIM ; Cheol-Kyu PARK ; Shin Yup LEE ; Min ki LEE ; Seong-Hoon YOON ; Jeong Eun LEE ; Sang Hoon LEE ; Seung Joon KIM ; Sung Yong LEE ; Jun Hyeok LIM ; Tae-Won JANG ; Seung Hun JANG ; Kye Young LEE ; Seung Hyeun LEE ; Sei Hoon YANG ; Dong Won PARK ; Chan Kwon PARK ; Hye Seon KANG ; Chang Dong YEO ; Chang-Min CHOI ; Jae Cheol LEE
Cancer Research and Treatment 2023;55(1):112-122
Purpose:
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods:
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results:
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.
10.Long-term cardiovascular events in hypertensive patients: full report of the Korean Hypertension Cohort
Jin Young LEE ; Jean Kyung BAK ; Mina KIM ; Ho-Gyun SHIN ; Kyun-Ik PARK ; Seung-Pyo LEE ; Hee-Sun LEE ; Ju-Yeun LEE ; Kwang-il KIM ; Si-Hyuck KANG ; Jang Hoon LEE ; Se Yong JANG ; Ju-Hee LEE ; Kye Hun KIM ; Jae Yeong CHO ; Jae-Hyeong PARK ; Sue K. PARK ; Hae-Young LEE
The Korean Journal of Internal Medicine 2023;38(1):56-67
Background/Aims:
This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension.
Methods:
The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension.
Results:
The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events.
Conclusions
This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.