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1.
Article in English | WPRIM | ID: wpr-787237

ABSTRACT

BACKGROUND/AIMS: This study aimed to identify the demographic and clinical factors associated with positive breath-test results and to assess the relationship between hydrogen and methane production in patients with suspected irritable bowel syndrome (IBS).METHODS: The demographic and clinical factors of 268 patients with suspected IBS, who had undergone a lactulose breath test, were analyzed.RESULTS: Of 268 patients included in this study, 143 (53.4%) were females. The median age and BMI of the patients was 58.0 years (range, 18.0–80.0 years) and 22.5 kg/m² (range, 14.4–34.3 kg/m²), respectively. A weak positive correlation was observed between the BMI and baseline hydrogen level (rho=0.134, p=0.031). Women were significantly more likely to show a ≥20 ppm increase in hydrogen within 90 min (early hydrogen increase, p=0.049), a ≥10 ppm increase in methane within 90 min (early methane increase, p=0.001), and a ≥10 ppm increase in methane between 90 min and 180 min (late methane increase, p=0.002) compared to men. The baseline hydrogen level was related to the baseline methane level (rho=0.592, p<0.001) and the maximal hydrogen level within 90 min was related to maximal methane level within 90 min (rho=0.721, p<0.001). Patients with an early hydrogen increase (43.8%) were more likely to show a positive result for an early methane increase compared to patients without an early increase in hydrogen (0%, p<0.001).CONCLUSIONS: Women were associated with high rates of positive lactulose breath-test results. In addition, methane production was correlated with hydrogen production.


Subject(s)
Breath Tests , Female , Humans , Hydrogen , Irritable Bowel Syndrome , Lactulose , Male , Methane , Sex Characteristics
2.
Cancer Research and Treatment ; : 1178-1187, 2020.
Article | WPRIM | ID: wpr-831138

ABSTRACT

Purpose@#Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Material and MethodsThis study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers. @*Results@#Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040). @*Conclusion@#MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

3.
Cancer Research and Treatment ; : 1086-1097, 2019.
Article in English | WPRIM | ID: wpr-763171

ABSTRACT

PURPOSE: Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS: We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS: The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION: Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Therapy , Humans , Immunohistochemistry , Neoadjuvant Therapy , Platinum , Prognosis , Retrospective Studies
4.
Cancer Research and Treatment ; : 1249-1256, 2019.
Article in English | WPRIM | ID: wpr-763155

ABSTRACT

PURPOSE: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. MATERIALS AND METHODS: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). RESULTS: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). CONCLUSION: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.


Subject(s)
Area Under Curve , Asian Continental Ancestry Group , Drug Therapy , Geriatric Assessment , Humans , Mass Screening , Prospective Studies , Sensitivity and Specificity
5.
Kosin Medical Journal ; : 1-14, 2019.
Article in English | WPRIM | ID: wpr-760468

ABSTRACT

OBJECTIVES: Intracoronary injection of acetylcholine (Ach) has been shown to induce significant coronary artery spasm (CAS) in patients with vasospastic angina. Clinical significance and angiographic characteristics of patients with ischemic electrocardiogram (ECG) changes during the Ach provocation test are not clarified yet. METHODS: A total 4,418 consecutive patients underwent coronary angiography with Ach provocation tests from 2004 to 2012 were enrolled. Ischemic ECG changes were defined as transient ST-segment depression or elevation ( > 1 mm) and T inversion with/without chest pain. Finally, a total 2,293 patients (28.5% of total subjects) proven CAS were enrolled for this study. RESULTS: A total 119 patients (5.2%) showed ECG changes during Ach provocation tests. The baseline clinical and procedural characteristics are well balanced between the two groups. Ischemic ECG change group showed more frequent chest pain, higher incidence of baseline spasm, severe vasospasm, multi-vessel involvement, and more diffuse spasm ( > 30 mm) than those without ischemic ECG changes. At 5 years, the incidences of death, major adverse cardiac events (MACE) and major adverse cardiac and cerebral events (MACCE) were higher in the ischemic ECG change group despite of optimal medical therapy. CONCLUSIONS: The patients with ischemic ECG changes during Ach provocation tests were associated with more frequent chest pain, baseline spasm, diffuse, severe and multi-vessel spasm than patients without ischemic ECG changes. At 5-years, the incidences of death, MACE and MACCE were higher in the ischemic ECG change group, suggesting more intensive medical therapy with close clinical follow up will be required.


Subject(s)
Acetylcholine , Chest Pain , Coronary Angiography , Coronary Vessels , Depression , Electrocardiography , Follow-Up Studies , Humans , Incidence , Spasm
6.
Article in English | WPRIM | ID: wpr-719427

ABSTRACT

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.


Subject(s)
Disease-Free Survival , Drug Therapy , Drug Therapy, Combination , Global Health , Humans , Korea , Observational Study , Prospective Studies , Quality of Life , Stomach Neoplasms , Weights and Measures
7.
Article in English | WPRIM | ID: wpr-713657

ABSTRACT

PURPOSE: Generally, adjuvant chemotherapy (AC) should be initiated as soon as possible after surgery to eradicate microscopic cancer cells. In this study, we investigated the effect of early AC on the survival of stage II/III gastric cancer patients. MATERIALS AND METHODS: Four hundred sixty patients who received AC (S-1 or XELOX) for pathologic stage II/III gastric cancer at Seoul National University Bundang Hospital between January 2008 and December 2014 were included. Patients were divided into 2 groups: early AC administration (within 4 weeks) and late AC administration (more than 4 weeks). Patients in the early AC group (n=174) were matched 1:1 with patients in the late AC group (n=174) by propensity scoring to adjust for clinical differences. Three-year relapse-free survival (RFS) was evaluated according to the timing of AC. RESULTS: Three-year RFS was 98.1% in stage IIA (n=109), 85.0% in stage IIB (n=83), 87.4% in stage IIIA (n=96), 83.5% in stage IIIB (n=91), and 62.5% in stage IIIC (n=81). After propensity score matching, RFS was similar between early and late AC groups (hazard ratio [HR],1.04; 95% confidence interval [CI], 0.62–1.74; P=0.889). Pathologic stage and histological type were independent prognostic factors of RFS (HR, 2.05; 95% CI, 1.06–3.96; P=0.033 and HR, 2.61; 95% CI, 1.42–4.80; P=0.002, respectively). CONCLUSIONS: Early initiation of AC within 4 weeks does not affect survival rates in stage II/III gastric cancer.


Subject(s)
Chemotherapy, Adjuvant , Drug Therapy , Humans , Propensity Score , Seoul , Stomach Neoplasms , Survival Rate
8.
Yonsei Medical Journal ; : 325-330, 2018.
Article in English | WPRIM | ID: wpr-713191

ABSTRACT

PURPOSE: To obtain validated clinical values suitable for developing a gustatory function test, including umami taste, in a Korean population. MATERIALS AND METHODS: The investigation involved 297 participants with self-reported normal sense of taste and smell. Liquid solutions were used for the assessment of gustatory function. The test consisted of 30 taste solutions [six concentrations of five tastants (sweet, bitter, salty, sour, and umami)]. For evaluation of overall gustatory function, the number of detected or correctly recognized taste thresholds was combined to form a “taste score.” RESULTS: Mean values of each detection and recognition threshold for the five tastes in men were consistently lower than those of women. The 10th percentile of taste score for recognition was used as the cut-off value for distinguishing normogeusia from hypogeusia. In subgroup analysis, total taste score from recognition thresholds revealed a significant negative correlation with age, indicating lower scores for increasing age. Taste score for non-smokers was significantly higher than that of smokers, in terms of detection and recognition of taste sensitivities. CONCLUSION: This gustatory function test was easy to perform, affordable, and time-saving, with the capacity to self-produce and obtain reliable data. Gustatory function was more sensitive in young people, women, and non-smokers.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Linear Models , Male , Middle Aged , Republic of Korea , Taste/physiology , Taste Threshold , Young Adult
9.
Yonsei Medical Journal ; : 90-98, 2017.
Article in English | WPRIM | ID: wpr-65058

ABSTRACT

PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography. CONCLUSION: Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.


Subject(s)
Acetylcholine , Aged , Angina Pectoris/diagnosis , Calcium Channel Blockers/therapeutic use , Cardiovascular Agents/therapeutic use , Coronary Angiography/adverse effects , Coronary Artery Disease/prevention & control , Coronary Vasospasm/diagnosis , Diltiazem/therapeutic use , Drug Therapy, Combination , Female , Humans , Incidence , Male , Middle Aged , Myocardial Infarction/prevention & control , Nitrates/therapeutic use , Propensity Score , Time Factors , Vasodilator Agents/therapeutic use
10.
Article in English | WPRIM | ID: wpr-105175

ABSTRACT

Variability in rapid response system (RRS) characteristics based on the admitted wards is unknown. We aimed to compare differences in the clinical characteristics of RRS activation between patients admitted to medical versus surgical services. We reviewed patients admitted to the hospital who were detected by the RRS from October 2012 to February 2014 at a tertiary care academic hospital. We compared the triggers for RRS activation, interventions performed, and outcomes of the 2 patient groups. The RRS was activated for 460 patients, and the activation rate was almost 2.3 times higher for surgical services than that for medical services (70% vs. 30%). The triggers for RRS activation significantly differed between patient groups (P = 0.001). They included abnormal values for the respiratory rate (23.2%) and blood gas analysis (20.3%), and low blood pressure (18.8%) in the medical group; and low blood pressure (32.0%), low oxygen saturation (20.8%), and an abnormal heart rate (17.7%) in the surgical group. Patients were more likely classified as do not resuscitate or required intensive care unit admission in the medical group compared to those in the surgical group (65.3% vs. 54.7%, P = 0.045). In multivariate analysis, whether the patient belongs to medical services was found to be an independent predictor of mortality after adjusting for the modified early warning score, Charlson comorbidity index, and intervention performed by the RRS team. Our data suggest that RRS triggers, interventions, and outcomes greatly differ between patient groups. Further research is needed to evaluate the efficacy of an RRS approach tailored to specific patient groups.

11.
Korean Circulation Journal ; : 795-810, 2017.
Article in English | WPRIM | ID: wpr-90215

ABSTRACT

Bioresorbable vascular scaffold (BRS) is an innovative device that provides structural support and drug release to prevent early recoil or restenosis, and then degrades into nontoxic compounds to avoid late complications related with metallic drug-eluting stents (DESs). BRS has several putative advantages. However, recent randomized trials and registry studies raised clinical concerns about the safety and efficacy of first generation BRS. In addition, the general guidance for the optimal practice with BRS has not been suggested due to limited long-term clinical data in Korea. To address the safety and efficacy of BRS, we reviewed the clinical evidence of BRS implantation, and suggested the appropriate criteria for patient and lesion selection, scaffold implantation technique, and management.


Subject(s)
Coronary Disease , Drug Liberation , Drug-Eluting Stents , Humans , Korea , Stents , Thrombosis
13.
Article in Korean | WPRIM | ID: wpr-139827

ABSTRACT

OBJECTIVES: The purpose of this study is to investigate the variables besides symptom that influence the family burden in the primary caregivers of remitted schizophrenic outpatients, and to evaluate the impact of changeable or unchangeable variables by clinical practice on the family burden. METHODS: A total 105 remitted schizophrenic outpatients and 105 their primary caregivers were participated in the psychiatric outpatient clinic of the university hospital. Socio-demographic characteristics (age, sex, education, income, marital status, religion), clinical variables (duration of illness, age of onset), patients' symptom (korean version of the positive and negative syndrome scale), patients' social function (korean version of the social functioning scale), patients' insight (self-appraisal of illness questionnaire), patients' attitude toward medication (drug attitude inventory), family perceived social support (multidimensional scale of perceived social support), family attitude toward patient (family attitude scale) were gathered from subjects. RESULTS: Total score of family burden scale (0–144) of the primary caregivers of remitted schizophrenic outpatients was 71.3 (SD 20.7) and mean score per item was 1.9. Unchangeable six variables by clinical practice (relation with patient, patients' education, age of onset, duration of illness, parent age, parent income) explain 17%, and changeable four variables (family attitude toward patient, family perceived social support, patients' social function, patients' insight) explain 72% of family burden. Four areas such as interpersonal communication, independence-performance, independence-competence, occupation/ employment explain family burden significantly in the seven areas of the social functioning scale. CONCLUSION: Primary caregivers of remitted schizophrenic outpatients feel burden considerably even though their ill relatives show few psychiatric symptoms. Changeable variables by clinical practice were more explanation than unchangeable variables on the family burden.


Subject(s)
Age of Onset , Ambulatory Care Facilities , Caregivers , Education , Employment , Humans , Marital Status , Outpatients , Parents , Schizophrenia
14.
Article in Korean | WPRIM | ID: wpr-139826

ABSTRACT

OBJECTIVES: The purpose of this study is to investigate the variables besides symptom that influence the family burden in the primary caregivers of remitted schizophrenic outpatients, and to evaluate the impact of changeable or unchangeable variables by clinical practice on the family burden. METHODS: A total 105 remitted schizophrenic outpatients and 105 their primary caregivers were participated in the psychiatric outpatient clinic of the university hospital. Socio-demographic characteristics (age, sex, education, income, marital status, religion), clinical variables (duration of illness, age of onset), patients' symptom (korean version of the positive and negative syndrome scale), patients' social function (korean version of the social functioning scale), patients' insight (self-appraisal of illness questionnaire), patients' attitude toward medication (drug attitude inventory), family perceived social support (multidimensional scale of perceived social support), family attitude toward patient (family attitude scale) were gathered from subjects. RESULTS: Total score of family burden scale (0–144) of the primary caregivers of remitted schizophrenic outpatients was 71.3 (SD 20.7) and mean score per item was 1.9. Unchangeable six variables by clinical practice (relation with patient, patients' education, age of onset, duration of illness, parent age, parent income) explain 17%, and changeable four variables (family attitude toward patient, family perceived social support, patients' social function, patients' insight) explain 72% of family burden. Four areas such as interpersonal communication, independence-performance, independence-competence, occupation/ employment explain family burden significantly in the seven areas of the social functioning scale. CONCLUSION: Primary caregivers of remitted schizophrenic outpatients feel burden considerably even though their ill relatives show few psychiatric symptoms. Changeable variables by clinical practice were more explanation than unchangeable variables on the family burden.


Subject(s)
Age of Onset , Ambulatory Care Facilities , Caregivers , Education , Employment , Humans , Marital Status , Outpatients , Parents , Schizophrenia
15.
Article in English | WPRIM | ID: wpr-167297

ABSTRACT

PURPOSE: This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen. MATERIALS AND METHODS: Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m² intravenously (IV) on D1 (D), docetaxel 60 mg/m² IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m2 IV D1 plus oral S-1 30 mg/m² twice a day on D1-14 (DS). RESULTS: Seventy-two patients were randomized to the D (n=23), DC (n=24), or DS (n=25) group. The confirmed response rate was 4.3% (95% confidence interval [CI], 0% to 12.6%), 4.3% (95% CI, 0% to 12.6%), and 8.7% (95% CI, 0% to 20.2%) for the D, DC, and DS groups, respectively. Compared to the D arm, the DS arm had a better progression-free survival (2.7 months vs. 1.3 months, p=0.034) without any deterioration in safety or quality of life, whereas the DC arm had a similar progression-free survival (1.8 months vs. 1.3 months, p=0.804) and poorer overall survival (5.6 months vs. 10.0 months, p=0.035). CONCLUSION: A re-challenge with S-1, but not cisplatin, in combination with docetaxel has potential anticancer benefits over docetaxel alone in MGC with progression after prior cisplatin plus S-1 or capecitabine.


Subject(s)
Antineoplastic Agents , Arm , Capecitabine , Cisplatin , Disease-Free Survival , Drug Therapy , Humans , Quality of Life , Stomach Neoplasms
16.
Yonsei Medical Journal ; : 9-18, 2017.
Article in English | WPRIM | ID: wpr-222311

ABSTRACT

PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.


Subject(s)
Adenocarcinoma/drug therapy , Cell Line, Tumor , Cetuximab/pharmacology , Drug Resistance, Neoplasm/drug effects , Epidermal Growth Factor/metabolism , Gene Rearrangement , Hepatocyte Growth Factor/pharmacology , Humans , Indoles/pharmacology , Lung Neoplasms/drug therapy , MAP Kinase Signaling System , Mutation , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Piperidines/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/antagonists & inhibitors , Pyrroles/pharmacology , Quinazolines/pharmacology , RNA, Small Interfering/pharmacology , ErbB Receptors/genetics , Signal Transduction/drug effects , fms-Like Tyrosine Kinase 3/metabolism
17.
Article in Korean | WPRIM | ID: wpr-645683

ABSTRACT

Conductive hearing loss is a condition that can be corrected surgically in most cases. Stapedotomy is usually performed for patients with congenital ossicular anomaly or fixation. However, otologic surgeons have often encountered difficulty due to the complexity of stapes surgery. Moreover, congenital stapes fixation with anomalous facial nerve and oval window absence is an uncommon and dangerous condition. In such cases, vestibulotomy can be a surgical option to prevent facial nerve damage and improve hearing. The etiology can be explained by the embryological development of the middle ear structures. To prevent facial nerve damage and maximize the efficacy of surgery, the surgeon should have knowledge about this disease and take a computed tomography for double check before stapes surgery. We describe a case of congenital stapes fixation with aberrant facial nerve courses, a 15-year-old female who was treated with vestibulotomy and piston wire insertion.


Subject(s)
Adolescent , Ear, Middle , Facial Nerve , Female , Hearing , Hearing Loss, Conductive , Humans , Oval Window, Ear , Stapes Surgery , Stapes , Surgeons
18.
Article in English | WPRIM | ID: wpr-64170

ABSTRACT

PURPOSE: HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in colorectal cancer (CRC) cell lines. MATERIALS AND METHODS: The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index. RESULTS: The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50 = 0.003 and 0.005 microM, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells. CONCLUSION: These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, singly or in combination with chemotherapeutic agents. The role of BMX expression as a marker of response to HM781-36B should be further explored.


Subject(s)
Apoptosis , Cell Cycle , Cell Line , Cell Survival , Colonic Neoplasms , Colorectal Neoplasms , Cytoplasm , Flow Cytometry , Fluorouracil , Humans , Phosphotransferases , Protein-Tyrosine Kinases , ErbB Receptors
19.
Korean Circulation Journal ; : 632-638, 2016.
Article in English | WPRIM | ID: wpr-62512

ABSTRACT

BACKGROUND AND OBJECTIVES: Cigarette smoking is a risk significant factor in coronary artery disease (CAD) and vasospastic angina (VSA). However, it is largely unknown whether smoking adds to any long-term clinical risk in VSA patients. SUBJECTS AND METHODS: A total of 2797 patients without significant CAD underwent acetylcholine (Ach) provocation test between November 2004 and October 2010. Patients were divided into three groups, based on the presence of coronary artery spasm (CAS) and smoking habits (non-CAS group: n=1188, non-smoking CAS group: n=1214, smoking CAS group: n=395). All CAS patients were prescribed with anti-anginal medications for at least 6 months. The incidence of major clinical outcomes and recurrent angina of these groups were compared up to 3 years. RESULTS: There were considerable differences in the baseline clinical and angiographic characteristics among the three groups, but there was no difference in the endpoints among the three groups (including individual and composite hard endpoints) such as death, myocardial infarction, de novo percutaneous coronary intervention, cerebrovascular accident, and major adverse cardiac events. However, there was a higher incidence of recurrent angina in both the non-smoking CAS group and smoking CAS group, as compared to the non-CAS group. In multivariable adjusted Cox-proportional hazards regression analysis, smoking CAS group exhibited a higher incidence of recurrent angina compared with the non-CAS group (hazard ratio [HR]; 2.46, 95% confidence interval [CI]; 1.46-4.14, p=0.001) and non-smoking CAS group (HR; 1.76, 95% CI; 1.08-2.87, p=0.021). CONCLUSION: Cigarette smoking CAS group exhibited higher incidence of recurrent angina during the 3-year clinical follow-up compared with both the non-CAS group and non-smoking CAS group. Quitting of smoking, paired with intensive medical therapy and close clinical follow-up, can help to prevent recurrent angina.


Subject(s)
Acetylcholine , Coronary Artery Disease , Coronary Vessels , Follow-Up Studies , Humans , Incidence , Myocardial Infarction , Percutaneous Coronary Intervention , Smoke , Smoking , Spasm , Stroke , Tobacco Products
20.
Article in English | WPRIM | ID: wpr-61886

ABSTRACT

PURPOSE: Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertainwhetherroutine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery. MATERIALS AND METHODS: This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A. RESULTS: The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age ≥ 70 years (odds ratio [OR], 5.61), ≥ 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/μL (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%). CONCLUSION: The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a risk-stratified basis.


Subject(s)
Asia , Asian Continental Ancestry Group , Cohort Studies , Colorectal Neoplasms , Colorectal Surgery , Comorbidity , Humans , Incidence , Leukocyte Count , Prospective Studies , Risk Factors , Thrombosis , Ultrasonography, Doppler , Veins , Venous Thromboembolism
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