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1.
Brain Stimul ; 17(5): 1060-1075, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218349

RESUMEN

BACKGROUND: Non-invasive deep brain modulation (DBM) stands as a promising therapeutic avenue to treat brain diseases. Acoustic DBM represents an innovative and targeted approach to modulate the deep brain, employing techniques such as focused ultrasound and shock waves. Despite its potential, the optimal mechanistic parameters, the effect in the brain and behavioral outcomes of acoustic DBM remains poorly understood. OBJECTIVE: To establish a robust protocol for the shock wave DBM by optimizing its mechanistic profile of external stimulation, and to assess its efficacy in preclinical settings. METHODS: We used shockwaves due to their capacity to leverage a broader spectrum of peak intensity (10-127 W/mm2) in contrast to ultrasound (0.1-5.0 W/mm2), thereby enabling a more extensive range of neuromodulation effects. We established various types of shockwave pressure profiles of DBM and compared neural and behavioral responses. To ascertain the anticipated cause of the heightened neural activity response, numerical analysis was employed to examine the mechanical dynamics within the brain. RESULTS: An optimized profile led to an enhancement in neuronal activity within the hypothalamus of mouse models. The optimized profile in the hippocampus elicited a marked increase in neurogenesis without neuronal damage. Behavioral analyses uncovered a noteworthy reduction in locomotion without significant effects on spatial memory function. CONCLUSIONS: The present study provides an optimized shock wave stimulation protocol for non-invasive DBM. Our optimized stimulation profile selectively triggers neural functions in the deep brain. Our protocol paves the way for new non-invasive DBM devices to treat brain diseases.

2.
Science ; 385(6707): 438-446, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38935778

RESUMEN

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective antiobesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to patients with obesity and observed a heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1 receptor (GLP-1R) neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified that an intricate interplay between DMHGLP-1R neurons and neuropeptide Y/agouti-related peptide neurons of the arcuate nucleus (ARCNPY/AgRP neurons) occurs to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering previously unexplored neural targets for obesity and metabolic diseases.


Asunto(s)
Núcleo Arqueado del Hipotálamo , Núcleo Hipotalámico Dorsomedial , Agonistas Receptor de Péptidos Similares al Glucagón , Obesidad , Saciedad , Animales , Femenino , Humanos , Masculino , Ratones , Proteína Relacionada con Agouti/metabolismo , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/metabolismo , Núcleo Hipotalámico Dorsomedial/efectos de los fármacos , Núcleo Hipotalámico Dorsomedial/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/fisiología , Neuropéptido Y/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/psicología , Optogenética , Saciedad/efectos de los fármacos , Agonistas Receptor de Péptidos Similares al Glucagón/administración & dosificación , Agonistas Receptor de Péptidos Similares al Glucagón/farmacología
3.
Nat Commun ; 14(1): 1486, 2023 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-36932069

RESUMEN

For survival, it is crucial for eating behaviours to be sequenced through two distinct seeking and consummatory phases. Heterogeneous lateral hypothalamus (LH) neurons are known to regulate motivated behaviours, yet which subpopulation drives food seeking and consummatory behaviours have not been fully addressed. Here, in male mice, fibre photometry recordings demonstrated that LH leptin receptor (LepR) neurons are correlated explicitly in both voluntary seeking and consummatory behaviours. Further, micro-endoscope recording of the LHLepR neurons demonstrated that one subpopulation is time-locked to seeking behaviours and the other subpopulation time-locked to consummatory behaviours. Seeking or consummatory phase specific paradigm revealed that activation of LHLepR neurons promotes seeking or consummatory behaviours and inhibition of LHLepR neurons reduces consummatory behaviours. The activity of LHLepR neurons was increased via Neuropeptide Y (NPY) which acted as a tonic permissive gate signal. Our results identify neural populations that mediate seeking and consummatory behaviours and may lead to therapeutic targets for maladaptive food seeking and consummatory behaviours.


Asunto(s)
Hambre , Receptores de Leptina , Ratones , Masculino , Animales , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Hipotálamo/metabolismo , Neuronas/metabolismo , Conducta Consumatoria , Leptina/metabolismo
4.
Int J Mol Sci ; 23(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36293050

RESUMEN

Cancer is the second-leading cause of death worldwide, and therapeutic peptides that target and destroy cancer cells have received a great deal of interest in recent years. Traditional wet experiments are expensive and inefficient for identifying novel anticancer peptides; therefore, the development of an effective computational approach is essential to recognize ACP candidates before experimental methods are used. In this study, we proposed an Ada-boosting algorithm with the base learner random forest called ACP-ADA, which integrates binary profile feature, amino acid index, and amino acid composition with a 210-dimensional feature space vector to represent the peptides. Training samples in the feature space were augmented to increase the sample size and further improve the performance of the model in the case of insufficient samples. Furthermore, we used five-fold cross-validation to find model parameters, and the cross-validation results showed that ACP-ADA outperforms existing methods for this feature combination with data augmentation in terms of performance metrics. Specifically, ACP-ADA recorded an average accuracy of 86.4% and a Mathew's correlation coefficient of 74.01% for dataset ACP740 and 90.83% and 81.65% for dataset ACP240; consequently, it can be a very useful tool in drug development and biomedical research.


Asunto(s)
Biología Computacional , Neoplasias , Humanos , Biología Computacional/métodos , Péptidos/química , Algoritmos , Aminoácidos/química , Neoplasias/tratamiento farmacológico
5.
Psychosom Med ; 81(1): 41-50, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30371632

RESUMEN

OBJECTIVE: Patients with advanced cancer commonly experience multiple symptoms that present as groups or clusters. The present study aimed to examine whether hypothalamus-pituitary-adrenal (HPA) axis dysfunction underlies the concurrent multiple symptoms in patients with advanced cancer. METHODS: Patients' cortisol levels were determined in saliva samples collected after awakening (0, 30, and 60 minutes after awakening) and at nighttime (21:00-22:00 PM) from 46 patients with lung cancer (15.2% women), with a mean (standard deviation) age of 64.3 (9.2) years and 47 healthy participants (53.2% women; age = 62.0 [4.6] years). Cancer-related symptoms were measured using the M.D. Anderson Symptom Inventory (MDASI). RESULTS: Compared with healthy participants, patients showed a significantly reduced cortisol awakening response (F(1,364) = 46.2, p < .001) and had flatter diurnal slope of cortisol (larger ß values) (mean [standard error of the mean] = -0.64 [0.06] versus -0.18 [0.05], p < .001). Altered HPA axis function was significantly and adversely associated with performance status and burden of symptoms (all p values < .01). However, each MDASI item varied widely in the degree of association with the HPA axis function. Hierarchical clustering analysis based on Spearman's rank correlation with complete linkage identified that nausea was clustered with vomiting, numbness, and dry mouth, whereas the other nine MDASI core symptoms associated with altered HPA axis function were clustered together. CONCLUSIONS: Altered HPA axis function may be a possible biological pathway that can explain the concurrence of core symptoms in patients with advanced lung cancer.


Asunto(s)
Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisario , Neoplasias Pulmonares , Sistema Hipófiso-Suprarrenal , Anciano , Femenino , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Saliva , Índice de Severidad de la Enfermedad
6.
Sci Rep ; 7(1): 1516, 2017 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-28473719

RESUMEN

An advanced organic photodetector (OPD) with a butter layer of Si-rich silicon oxynitride (SiOxNy) was fabricated. The detector structure is as follows: Indium tin oxide (ITO) coated glass substrate/SiOxNy(10 nm)/naphthalene-based donor:C60(1:1)/ITO. Values of x and y in SiOxNy were carefully controlled and the detector performances such as dark current and thermal stability were investigated. When the values of x and y are 0.16 and 0.66, the detector illustrates low dark current as well as excellent thermal stability. In the OPD, silicon oxynitride layer works as electron barrier under reverse bias, leading to the decrease of dark current and increase of detectivity. Since the band gap of silicon oxynitride unlike conventional buffer layers can also be controlled by adjusting x and y values, it can be adapted into various photodiode applications.

7.
Clin Lung Cancer ; 18(4): e289-e296, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28185792

RESUMEN

INTRODUCTION: To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non-small-cell lung cancer. MATERIALS AND METHODS: A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m2 with either docetaxel 60 mg/m2 (n = 71) or pemetrexed 500 mg/m2 (n = 77) for ≤ 4 cycles. The primary objective was to assess the noninferiority of progression-free survival (PFS) for patients receiving the Doc-Cis regimen. The secondary endpoints were the response rates, overall survival, and toxicity profiles. RESULTS: Partial remission was observed in 24 (31.2%) and 24 (33.8%) patients in the Pem-Cis and Doc-Cis groups, respectively. The median PFS was 4.7 months (95% confidence interval [CI], 4.4-5.0) in the Pem-Cis arm and 4.4 months (95% CI, 3.7-5.1) in the Doc-Cis arm (P > .05). The median overall survival was longer in the Doc-Cis arm (13.3 months; 95% CI, 8.1-18.5) than in the Pem-Cis arm (11.7 months; 95% CI, 8.6-14.8; P > .05). Between the 2 arms, no significant difference was found in the subsequent treatments after failure of first-line treatment. The rate of grade 3 or 4 neutropenia and febrile neutropenia was greater in the Doc-Cis arm than in the Pem-Cis arm. CONCLUSION: In nonsquamous non-small-cell lung cancer patients lacking driver mutations, the PFS and response rates were similar between the 2 arms, and toxicity was tolerable, although adverse events and more severe toxicities were observed more frequently in the Doc-Cis arm.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Pemetrexed/uso terapéutico , Taxoides/uso terapéutico , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Docetaxel , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neutropenia/etiología , Análisis de Supervivencia , Resultado del Tratamiento
8.
BMC Cancer ; 16: 690, 2016 08 26.
Artículo en Inglés | MEDLINE | ID: mdl-27566413

RESUMEN

BACKGROUND: No novel chemotherapeutic combinations have demonstrated superior efficacy to etoposide/cisplatin (EP), a standard treatment regimen for extensive-stage small cell lung carcinoma (ES-SCLC) over the past decade. We aimed to compare the efficacy and safety of belotecan/cisplatin (BP) and EP regimens in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC. METHODS: We conducted a multi-center, randomized, open-label, parallel-group, phase III clinical study. A total of 157 patients were recruited at 14 centers with 147 patients meeting the inclusion/exclusion criteria and randomized to either BP (n = 71) or EP (n = 76) treatment arms. A non-inferior response rate (RR) in the BP arm, analyzed by intent-to-treat analysis according to Response Evaluation Criteria in Solid Tumors version 1.0 criteria, was used as the primary endpoint. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: In the BP arm, one patient had a complete response, 41 had a partial response (PR), and 17 had stable disease (SD). In the EP arm, 35 patients had PR and 28 had SD. The RR in the BP arm was non-inferior to the EP regimen in patients with ES-SCLC (BP: 59.2 %, EP: 46.1 %, difference: 13.1 %, 90 % two-sided confidence interval: -0.3-26.5, meeting the predefined non-inferiority criterion of -15.0 %). No significant differences in OS or PFS were observed between the treatment arms. Hematologic toxicities, including grade 3/4 anemia and thrombocytopenia, were significantly more prevalent in the BP arm than the EP arm. CONCLUSIONS: The RR to the BP regimen was non-inferior to the EP regimen in chemotherapy- and radiotherapy-naïve patients with previously untreated ES-SCLC. Hematologic toxicities were significantly more prevalent in the BP group, indicating that BP should be used with care, particularly in patients with a poor performance status. Further studies assessing PFS and OS are required to validate the superiority of the BP regimen. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00826644 . Date of Registration: January 21, 2009.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Carcinoma de Células Pequeñas/mortalidad , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad
9.
Jpn J Clin Oncol ; 46(2): 144-51, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26590014

RESUMEN

OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. METHODS: We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. RESULTS: Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). CONCLUSION: Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Radioterapia Conformacional , Adulto , Anciano , Anciano de 80 o más Años , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Modelos de Riesgos Proporcionales , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Taxoides/administración & dosificación , Resultado del Tratamiento , Gemcitabina
10.
Clin Exp Otorhinolaryngol ; 8(4): 396-401, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26622961

RESUMEN

OBJECTIVES: Argon plasma coagulation (APC) is a noncontact form of electrocautery that utilizes ionized argon as the electrical current. A rigid bronchoscopic use of APC for the management of central airway obstruction could be safe and rapidly effective. This study evaluated the usefulness of rigid bronchoscopy with APC for the management of central airway obstructions due to benign or malignant tumors. METHODS: Twenty patients with obstructing central airway tumors were retrospectively reviewed from February 2008 to February 2013 at Chonnam National University Hospital. All patients received rigid bronchoscopic tumor removal under general anesthesia. APC was applied before and after tumor removal. RESULTS: The median age of patients was 59 years (interquartile range [IQR], 51 to 67 years) and 70% were female. The causes of airway obstruction included malignancy (n=8) and benign tumor (n=12). Airway tumors comprised intraluminal lesions (n=11, 55%) and mixed intraluminal/extraluminal lesions (n=9, 45%). The median tumor size was 15 mm (IQR, 10 to 18 mm). The median degree of airway obstruction was significantly reduced after intervention (90% [IQR, 88% to 96%] vs. 10% [IQR, 0% to 20%], P<0.001). The median American Thoracic Society dyspnea grade (3 [IQR, 1 to 4] vs. 1 [IQR, 0 to 1], P<0.001) and forced expiratory volume in one second (1.03 L [IQR, 0.52 to 1.36 L] vs. 1.98 L [IQR, 1.57 to 2.64 L], P=0.004) were significantly improved after intervention. There were no procedure-related acute complications and deaths. CONCLUSION: Rigid bronchoscopy with APC is an effective and safe procedure to alleviate central airway obstruction caused by tumors.

11.
Thorac Cancer ; 6(6): 800-4, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26557922

RESUMEN

Several cases of acquired resistance in patients with activating epidermal growth factor receptor (EGFR) mutation have been reported. However, rare clinical cases exist of a transformation to small cell lung cancer (SCLC) following treatment with EGFR-tyrosine kinase inhibitors (TKIs). We report a case of non-small cell lung cancer (NSCLC) with L858R mutation at the time of diagnosis. After failure of EGFR-TKI therapy, we performed additional histopathologic examinations. We confirmed that the patient had a histological transformation from NSCLC to SCLC. We performed chemotherapy with etoposide and cisplatin against the SCLC and radiologic findings were improved.

12.
Thorac Cancer ; 6(2): 224-6, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26273363

RESUMEN

We report a case showing the long-term clinical benefit of the continued use of gefitinib in a patient with asymptomatic progression of lung adenocarcinoma harboring an exon 19 deletion of the epidermal growth factor receptor gene. Although follow-up studies showed smoldering progression of metastatic lesions, continued treatment with gefitinib controlled pulmonary adenocarcinoma for more than six years.

13.
Complement Ther Med ; 23(3): 381-7, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26051573

RESUMEN

OBJECTIVE: To investigate the effect of combining conventional treatment with regional hyperthermia on cancer pain in lung cancer patients. DESIGN: Case-control study. SETTING: One Korean university hospital and three complementary cancer clinics. MAIN OUTCOMES AND MEASURES: Main outcome was effective analgesic score (EAS, PI[1+(M/10)], 1: anti-inflammatory drug consumption at a regular dosage, M: weekly dose (mg) of oral morphine equivalent and PI: pain intensity) at four time points (baseline (days -30 to 0), time 1 (days 1-60), time 2 (days 61-120), and time 3 (days 121-180)). Propensity score matching between the hyperthermia and control groups was performed using a 1:5 ratio. A linear mixed effects model was employed to measure EAS changes over time in the two groups. RESULTS: At baseline, there were 83 subjects in the control group and 32 subjects in the hyperthermia group. At time 3, there were 49 subjects in the control group and 16 subjects in the hyperthermia group. Analyses showed rate of change of EAS, treatment×time was significant (p=0.038). This significant difference was mainly observed for time 1 (mean difference: 101.76 points, 95% confidence interval: 10.20-193.32 points, p=0.030). CONCLUSIONS: Our results indicate an increase in cancer pain in lung cancer patients administered regional hyperthermia, particularly during the early stage of hyperthermia treatment.


Asunto(s)
Hipertermia Inducida/métodos , Neoplasias Pulmonares/complicaciones , Manejo del Dolor/métodos , Dolor , Anciano , Analgésicos Opioides/uso terapéutico , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfina/uso terapéutico , Dolor/etiología , Dolor/fisiopatología , Resultado del Tratamiento
14.
J Thorac Dis ; 7(3): 433-8, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25922722

RESUMEN

BACKGROUND: Tegafur-uracil (UFT) is an anticancer agent that inhibits thymidylate synthase (TS). The degree of TS expression in primary lung cancer (LC) is different according to histologic cell type. In this study, we examined the variability of the anti-tumor efficacy of UFT monotherapy depending on histological subtypes of LC. METHODS: In the current single-institution, retrospective study, we assigned the patients with LC to three histologic groups [the squamous (Sq) non-small cell lung cancer (NSCLC)] group, the non-Sq NSCLC group and the SCLC group] and then compared the clinical response to UFT monotherapy between the three groups. RESULTS: Our clinical series of 149 patients include 54 cases of Sq NSCLC, 67 cases of non-Sq NSCLC and 28 cases of SCLC. For Sq NSCLC, non-Sq NSCLC and SCLC group, the overall response rates (ORRs) were 1%, 1% and 0% (P=0.522), respectively. The disease control rates (DCRs) were 38.9%, 31.3% and 10.7% (P=0.012), respectively. The median progression-free survivals (PFSs) were 2.68, 2.25 and 1.46 months (P=0.004 for three groups and P=0.773 for two groups except for the SCLC group at the log-rank test), respectively. There was no significant difference between the groups in median overall survival (OS). CONCLUSIONS: Our results indicate that the degree of the anti-tumor effect of UFT was higher in patients with NSCLC as compared with SCLC. But it showed no significant difference between the patients with Sq NSCLC and those with non-Sq NSCLC.

15.
Cancer Res Treat ; 47(4): 661-9, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25715768

RESUMEN

PURPOSE: Direct sequencing (DS) is the standard method for detection of epidermal growth factor receptor (EGFR) gene mutation in non-small cell lung cancer (NSCLC); however, low detection sensitivity is a problem. The aim of this study is to demonstrate higher detection rate of EGFR gene mutation with peptide nucleic acid (PNA) clamping compared with DS. MATERIALS AND METHODS: This is a single arm, prospective study for patients with stage IIIB/IV or relapsed NSCLC. Using tumor DNA from 138 patients, both DS and PNA clamping for EGFR gene in exon 18, 19, 20, and 21 were performed. Discrepant results between the two methods were verified using Cobas and a mutant enrichment based next generation sequencing (NGS). Patients with activating mutations were treated with EGFR tyrosine kinase inhibitor (EGFR-TKI, gefitinib, or erlotinib) as first line treatment. RESULTS: Of 138 paired test sets, 24 (17.4%) and 45 (32.6%) cases with activating mutations were detected by DS and PNA clamping, respectively. The difference of detection rate between the two methods was 15.2% (95% confidence interval, 8.7% to 17.8%; p < 0.001). Between the two methods, 25 cases showed discrepant results (n=23, PNA+/DS-; n=2, PNA-/DS+). Mutations were confirmed by Cobas or NGS in 22 of 23 PNA+/DS- cases. The response rates to EGFR-TKI were 72.2% in the PNA+/DS+ group and 85.0% in the PNA+/DS- group. CONCLUSION: PNA clamping showed a significantly higher detection rate of EGFR gene mutation compared with DS. Higher sensitivity of PNA clamping was not compromised by the loss of predictive power of response to EGFR-TKI.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Análisis Mutacional de ADN/métodos , Receptores ErbB/genética , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Ácidos Nucleicos de Péptidos/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto Joven
16.
Sci Rep ; 5: 7708, 2015 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-25578322

RESUMEN

Complementary metal-oxide-semiconductor (CMOS) colour image sensors are representative examples of light-detection devices. To achieve extremely high resolutions, the pixel sizes of the CMOS image sensors must be reduced to less than a micron, which in turn significantly limits the number of photons that can be captured by each pixel using silicon (Si)-based technology (i.e., this reduction in pixel size results in a loss of sensitivity). Here, we demonstrate a novel and efficient method of increasing the sensitivity and resolution of the CMOS image sensors by superposing an organic photodiode (OPD) onto a CMOS circuit with Si photodiodes, which consequently doubles the light-input surface area of each pixel. To realise this concept, we developed organic semiconductor materials with absorption properties selective to green light and successfully fabricated highly efficient green-light-sensitive OPDs without colour filters. We found that such a top light-receiving OPD, which is selective to specific green wavelengths, demonstrates great potential when combined with a newly designed Si-based CMOS circuit containing only blue and red colour filters. To demonstrate the effectiveness of this state-of-the-art hybrid colour image sensor, we acquired a real full-colour image using a camera that contained the organic-on-Si hybrid CMOS colour image sensor.

17.
J Thorac Dis ; 6(9): 1209-17, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25276362

RESUMEN

BACKGROUND: With the recent increased use of new anti-neoplastic agents, molecular-targeted drugs and radiation in patients with lung cancer, there has been an increase in the occurrence drug-induced or radiation-induced pulmonary toxicities. We conducted this study to evaluate the clinical characteristics of patients with lung cancer who presented with treatment-related pulmonary toxicities and to analyze the dosage pattern of corticosteroid therapy against them. METHODS: To collect the baseline data from the patients with lung cancer who developed treatment-related pulmonary toxicities, we initially selected those who were prescribed corticosteroids between January 1, 2008 and December 31, 2012. Depending on clinical and radiological diagnoses, we classified pulmonary toxicities into drug-induced interstitial lung disease (DILD), radiation pneumonitis, acute exacerbation of chronic obstructive pulmonary disease (AE COPD) and others. RESULTS: We divided total patients (n=398) into four groups, and these include 88 cases (22%) of DILD, 189 cases (47%) of radiation pneumonitis, 47 cases (12%) of AE COPD and 74 cases (19%) of others. The prescribed rate of pulse or high-dose steroid was measured as 73%, 20%, 40% and 38%, respectively (P<0.001). In DILD radiologic findings, the 2-month mortality was significantly higher in the patients with the diffuse alveolar damage (DAD) pattern (100%) as compared with those with the non-specific interstitial pneumonia (NSIP) or bronchiolitis obliterans with organizing pneumonia (BOOP) one (62% or 42%, respectively) (P=0.032). CONCLUSIONS: This study showed that the natural course of DILD had more unfavorable outcome requiring higher dose steroid therapy as compared with those with radiation pneumonitis or AE COPD. According to a subgroup analysis of the patients with DILD, BOOP and NSIP radiographic patterns showed more favorable outcomes.

18.
Anticancer Res ; 34(9): 4939-48, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25202076

RESUMEN

BACKGROUND: To identify differentially expressed genes between parent and radioresistant lung cancer cell lines established by fractionated irradiation. MATERIALS AND METHODS: Lung cancer cell lines (A549, NCI-H1650) were irradiated with several fractionation schemes. Clonogenic assays were used to identify radioresistant cell lines. We compared the gene expression profiles on a cDNA microarray. RESULTS: Four established cell (A549-2G, A549-5G, H1650-2G and H1650-5G) were shown to be radioresistant (p≤0.05). Seventy-two genes were commonly altered in A549-G and 655 genes in H1650-G, compared to their parental cells. Genes in the wingless-type MMTV integration site family (WNT) signaling pathway were the ones most frequently altered in both A549-G and H1650-G cells. Those involved in inflammation; integrin, platelet-derived growth factor (PDGF), interleukin, transforming growth factor-beta (TGFB), epidermal growth factor receptor (EGFR) signaling, were commonly altered in radioresistant H1650 sublines. CONCLUSION: The major gene expression changes during irradiation are related to WNT signaling pathway.


Asunto(s)
Fraccionamiento de la Dosis de Radiación , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Neoplasias Pulmonares/genética , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Análisis por Conglomerados , Relación Dosis-Respuesta en la Radiación , Humanos , Neoplasias Pulmonares/radioterapia , Tolerancia a Radiación/genética , Reproducibilidad de los Resultados
19.
J Bronchology Interv Pulmonol ; 21(3): 230-3, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24992132

RESUMEN

Endobronchial pleomorphic adenoma is an extremely rare condition. A 32-year-old woman with exertional dyspnea and cough presented with a carinal mass on chest CT scan. The tumor was successfully removed by rigid bronchoscopy using argon plasma coagulation. Biopsy confirmed the diagnosis of pleomorphic adenoma.


Asunto(s)
Adenoma Pleomórfico/cirugía , Broncoscopía , Neoplasias de la Tráquea/cirugía , Adenoma Pleomórfico/diagnóstico por imagen , Adenoma Pleomórfico/patología , Adulto , Coagulación con Plasma de Argón , Femenino , Humanos , Tomografía Computarizada por Rayos X , Neoplasias de la Tráquea/diagnóstico por imagen , Neoplasias de la Tráquea/patología
20.
J Korean Med Sci ; 29(6): 825-30, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24932085

RESUMEN

Chronic sputum is a troublesome symptom in many respiratory diseases. The prevalence of chronic sputum varies from 1.2% to 13% according to the country. The purpose of this study was to estimate the prevalence of chronic sputum and to find its associated factors in a general Korean population. We analyzed the data of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A total number of 6,783 subjects aged 40 yr or more were enrolled in this study with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was 6.3% (n=430). Significant risk factors for chronic sputum by multivariate analysis were: age (≥ 70 yr) (odds ratio [OR], 1.954; 95% confidence interval [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of chronic sputum in Korea was in the intermediate range compared with other countries. Smoking is a preventable risk factor identified in this study, and major respiratory diseases, such as COPD and tuberculosis, should be considered in subjects with chronic sputum.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Esputo , Tuberculosis/epidemiología , Adulto , Anciano , Enfermedad Crónica , Demografía , Femenino , Humanos , Modelos Logísticos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , República de Corea , Factores de Riesgo , Fumar , Esputo/microbiología , Encuestas y Cuestionarios , Tuberculosis/fisiopatología
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