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1.
Ann Neurol ; 95(6): 1040-1054, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38520151

RESUMEN

OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.


Asunto(s)
CADASIL , Hemorragia Cerebral , Mutación , Receptor Notch3 , Humanos , Masculino , Femenino , Receptor Notch3/genética , Persona de Mediana Edad , CADASIL/genética , Estudios Retrospectivos , Hemorragia Cerebral/genética , Anciano , Mutación/genética , Adulto , Japón , República de Corea , Pueblo Asiatico/genética
2.
3.
Sensors (Basel) ; 23(2)2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36679678

RESUMEN

The light intensity and color temperature of natural light periodically change and promote the circadian entrainment of the human body. In addition, the color temperature cycle of natural light that is unique to each region is formed by its location and geographic and environmental factors, affecting the health of its residents. Research on lighting and construction to provide the color temperature of real-time natural light has continued to provide the beneficial effect of natural indoor lighting. However, lighting technology that provides the real-time color temperature of natural light could not be realized since it is challenging to select a color temperature cycle zone due to abrupt color temperature changes at sunrise and sunset. Such drastic shifts cause an irregular measurement of color temperature over time due to general weather or atmospheric conditions. In a previous study, a method of generating a color temperature cycle using deep learning was introduced, but the performance at the beginning and end of the color temperature cycle was unreliable. Therefore, this study proposes generating a real-time natural light color temperature cycle for the circadian lighting service. The characteristics of the daily color temperature cycle were analyzed based on the measured natural light characteristics database, and a data set for learning was established. To improve the color temperature cycle generation performance, a deep learning (TadGAN) model was implemented by searching for the lowest point of the color temperature at the start and end points of the color temperature cycle and applying the boot and ending datasets to these points. The color temperature cycle zone was accurately detected in real-time in the experiment, and the generation performance of the color temperature cycle was maintained at the beginning and end of the color temperature cycle. The mean absolute error decreased by about 67%, confirming the generation of a more accurate real-time color temperature cycle.


Asunto(s)
Luz , Iluminación , Humanos , Temperatura , Temperatura Corporal , Clima , Ritmo Circadiano , Color
4.
Sensors (Basel) ; 22(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36298124

RESUMEN

This study to develop lighting is advanced for reproducing natural light color temperature beneficial to humans. Methods were introduced to provide daily color temperature cycles through formulas based on the measured natural light characteristics or real-time reproduction of natural light color temperature linking sensors. Analysis results for the measured natural light showed that irregular color temperature cycles were observed for more than 90% of the year due to the influence of regional weather and atmospheric conditions. Regular color temperature cycles were observed only on some clear days. The color temperature cycle dramatically affects the health of the occupants. However, since irregular color temperatures are difficult to predict and cannot easily generate cycles, only the color temperatures of some clear days are currently used, and the actual color temperature of natural light cannot be reproduced. There is little research on deriving real-time periodic characteristics and lighting services targeting irregular color temperatures of natural light. Therefore, this paper proposes a TadGAN (Time Series Anomaly Detection Using Generative Adversarial Networks)-based daily color temperature cycle generation method that responds to irregular changes in the natural light color temperature. A TadGAN model for generating the natural light color temperature cycle was built, and learning was performed based on the dataset extracted through the measured natural light characteristic Database. After that, the generator of TadGAN was repeatedly applied to generate a color temperature cycle close to the change of natural light. In the performance test of the proposed method, it was possible to generate periodic characteristics of the irregular natural light color temperature distribution.


Asunto(s)
Luz , Iluminación , Humanos , Temperatura , Iluminación/métodos , Factores de Tiempo , Color
5.
Sensors (Basel) ; 21(22)2021 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-34833842

RESUMEN

As outdoor activities are necessary for maintaining our health, research interest in environmental conditions such as the weather, atmosphere, and ultraviolet (UV) radiation is increasing. In particular, UV radiation, which can benefit or harm the human body depending on the degree of exposure, is recognized as an essential environmental factor that needs to be identified. However, unlike the weather and atmospheric conditions, which can be identified to some extent by the naked eye, UV radiation corresponds to wavelength bands that humans cannot recognize; hence, the intensity of UV radiation cannot be measured. Recently, although devices and sensors that can measure UV radiation have been launched, it is very difficult for ordinary users to acquire ambient UV radiation information directly because of the cost and inconvenience caused by operating separate devices. Herein, a deep neural network (DNN)-based ultraviolet index (UVI) calculation method is proposed using representative color information of sun object images. First, Mask-region-based convolutional neural networks (R-CNN) are applied to sky images to extract sun object regions and then detect the representative color of the sun object regions. Then, a deep learning model is constructed to calculate the UVI by inputting RGB color values, which are representative colors detected later along with the altitude angle and azimuth of the sun at that time. After selecting each day of spring and autumn, the performance of the proposed method was tested, and it was confirmed that accurate UVI could be calculated within a range of mean absolute error of 0.3.


Asunto(s)
Rayos Ultravioleta , Tiempo (Meteorología) , Clima , Humanos , Redes Neurales de la Computación , Estaciones del Año
6.
Heliyon ; 7(6): e07350, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34195446

RESUMEN

The development of cerebral organoid technology has allowed the human neural tissue to be collected for studying human brain development and neurological diseases. Human pluripotent stem cell-derived cerebral organoids (hCOs) are a theoretically infinite source of fresh human brain tissue for various research purposes. However, hCOs have limitations, including core necrotic cell death. To solve this problem, we tested a simple method, which has been previously overlooked. In this study, we mechanically cut 70-day-old hCOs with a scalpel blade into 2 to 4 pieces, each depending on their original size. After culturing cut hCOs for additional 7 days, their size was less variable and smaller than uncut hCOs and there were no histological differences between uncut and cut hCOs. Note that hypoxia-inducible factor (HIF)-1α was expressed in the central area of uncut hCOs but not in cut hCOs. Uncut hCOs, therefore, showed broad core areas stained with terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL), whereas cut hCOs did not. In conclusion, this simple mechanical cutting method allowed us to acquire a larger number of hCOs without a necrotic core.

7.
Sensors (Basel) ; 21(4)2021 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-33572393

RESUMEN

Ultraviolet rays are closely related with human health and, recently, optimum exposure to the UV rays has been recommended, with growing importance being placed on correct UV information. However, many countries provide UV information services at a local level, which makes it impossible for individuals to acquire user-based, accurate UV information unless individuals operate UV measurement devices with expertise on the relevant field for interpretation of the measurement results. There is a limit in measuring ultraviolet rays' information by the users at their respective locations. Research about how to utilize mobile devices such as smartphones to overcome such limitation is also lacking. This paper proposes a mobile deep learning system that calculates UVI based on the illuminance values at the user's location obtained with mobile devices' help. The proposed method analyzed the correlation between illuminance and UVI based on the natural light DB collected through the actual measurements, and the deep learning model's data set was extracted. After the selection of the input variables to calculate the correct UVI, the deep learning model based on the TensorFlow set with the optimum number of layers and number of nodes was designed and implemented, and learning was executed via the data set. After the data set was converted to the mobile deep learning model to operate under the mobile environment, the converted data were loaded on the mobile device. The proposed method enabled providing UV information at the user's location through a mobile device on which the illuminance sensors were loaded even in the environment without UVI measuring equipment. The comparison of the experiment results with the reference device (spectrometer) proved that the proposed method could provide UV information with an accuracy of 90-95% in the summers, as well as in winters.

8.
Sensors (Basel) ; 20(22)2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-33218101

RESUMEN

The characteristics of natural light are mostly collected through specialized measuring equipment, such as a spectroradiometer, and some suggested measurement methods through a small RGB sensor. However, specialized measuring equipment presents difficulty in its high cost, and the RGB-sensor-based method has the limitation of being unable to measure the wavelength characteristics of natural light that are needed to implement lighting that supports circadian rhythms. This paper presents a method for calculating the short-wavelength-ratio-based color temperature of natural light in real time. First, an analysis of the correlation between the characteristics of natural light collected through a spectroradiometer was performed to determine the factors that were needed to accurately measure the color temperature of natural light. Then, the short-wavelength ratio of natural light was calculated through chromaticity coordinates (x and y), which are output values of the RGB sensor, and an equation for calculating the color temperature of natural light was derived through the short-wavelength ratio. Furthermore, after producing an RGB-sensor-based device, the derived equation was applied to calculate the color temperature of real-time natural light that reflects the wavelength characteristics. Then, as a result of the performance evaluation of the proposed method, the color temperature of natural light was accurately calculated within 1% of the average error rate.

9.
Sci Rep ; 10(1): 3684, 2020 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-32111890

RESUMEN

Porphyra 334 (P334), a mycosporine-like amino acid (MAA), is a secondary metabolite found in diverse marine and terrestrial organisms and has several beneficial effects on fibroblast proliferation, wound healing, and antioxidant activity. Here, we report that P334 accelerates the cell reprogramming process of mouse tail-tip fibroblasts (TTFs) and human dermal papilla (HDP) cells into induced pluripotent stem cells (iPSCs). We found that P334 significantly improved the cell reprogramming efficiency by activating the tri-methylation of histone 3 lysine 4 (H3K4me3), which controls mesenchymal to epithelial transition (MET) during the reprogramming process. Thus, we found that P334 directly regulates epigenetic changes, providing an efficient approach for natural compound-based cell reprogramming.


Asunto(s)
Técnicas de Reprogramación Celular , Reprogramación Celular/efectos de los fármacos , Ciclohexanonas/farmacología , Fibroblastos/metabolismo , Glicina/análogos & derivados , Células Madre Pluripotentes Inducidas/metabolismo , Animales , Fibroblastos/citología , Glicina/farmacología , Humanos , Células Madre Pluripotentes Inducidas/citología , Ratones
10.
J Psychiatr Res ; 118: 31-37, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31476707

RESUMEN

BACKGROUND: The cost-effectiveness of both cholinesterase inhibitors and memantine by delaying nursing home placement has been supported by numerous studies. The importance of sustained pharmacological treatment in dementia has been relatively less recognized by public health policies compared to early diagnosis. We investigated the effect of the drug (donepezil, rivastigmine, galantamine, and memantine) compliance on the health care costs in newly-diagnosed dementia. METHODS: National Health Insurance Service (NHIS) database which covers the entire population of South Korea was used for analysis. Health care expenditure of patients newly-diagnosed with dementia in between 2012 and 2014 was investigated for 3-5 years. For drug compliance, we used Medication Possession Ratio (MPR) that indicates the percentage of time a patient has access to medication. Multivariate linear regression analysis including generalized estimated equation and gamma distribution was used for statistical analysis. RESULTS: We identified 252,594 patients who were both prescribed with cognitive enhancers and newly diagnosed with dementia. When initial MPR increased 20%, total health care costs decreased 8.4% (RR = 0.916, 95%; CI 0.914 to 0.916). Same relationship was shown with medical costs related to dementia, admission to a general hospital, and emergency room visits. When MPR increased 20% compared to the previous year, the total health care costs, admission to a general hospital, emergency room visits, and admission to a nursing hospital decreased. CONCLUSIONS: This population-based retrospective cohort study provides evidence that patients newly-diagnosed with dementia who showed higher initial drug compliance or maintained antidementia drugs (Cholinesterase inhibitors and memantine) would benefit in total health-care costs.


Asunto(s)
Inhibidores de la Colinesterasa/uso terapéutico , Demencia/tratamiento farmacológico , Costos de la Atención en Salud/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Cumplimiento de la Medicación/estadística & datos numéricos , Programas Nacionales de Salud/estadística & datos numéricos , Nootrópicos/uso terapéutico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , República de Corea , Estudios Retrospectivos
11.
Sensors (Basel) ; 19(4)2019 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-30781754

RESUMEN

Ultraviolet (UV) rays are electromagnetic waves that account for about 5% of solar light, and when overexposed, they pose malevolent effects on human skin and health. However, with recent reports on the beneficial effects of some wavelength bands of UV rays, people's interest in UV information has increased. This has resulted in requiring not just simple information, such as the amount of UV or UV index (UVI), but detailed UV information that directly affects health, such as EUVB (erythemally weighted UVB). However, calculating EUVB, which can be done by applying the erythemal weighted function on the intensity value in wavelength, requires specialized optical measurement devices, which cannot be easily accessed by the general public; furthermore, public institutions' UV information services do not offer EUVB information for individuals. Therefore, the present study proposes a UVI sensor-based portable measurement device, with which the general public can have easy access to UV-related information. The proposed device comprises a UVI sensor that can measure the intensity of erythemal UV radiation, a Bluetooth Low Energy (BLE) module that supports communication, and a micro controller unit (MCU) for key operations. In addition, it applies the ratio of EUVB by month/time, resulting from the actual analysis of natural light to calculate the EUVB and provides the amount of UVI and EUVB to check if they meet conditions required for outdoor activities through the device and smartphone applications. The applicability of the proposed device was verified by the measurement performance comparison test with the standard device, a spectrometer (CAS 140 CT), which showed an average error of 0.045 for UVI and 0.0014 W/m². The proposed device's offering of UV-related information such as UVI and EUVB to the user is expected to prevent potential damage due to exposure to UV and to support healthy outdoor activities.

12.
Korean J Anesthesiol ; 72(1): 4-12, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30139213

RESUMEN

Delirium can be defined as an 'acute brain dysfunction.' Compared to dementia, which is a disease that deteriorates the brain function chronically, delirium shows very similar symptoms but is mostly ameliorated when the causative factors are normalized. Due to the heterogeneity in etiologies and symptoms, people including health care workers often mistake delirium for dementia or other psychiatric disorders. Delirium has attracted global interest increasingly and a vast amount of research on its management has been conducted. Experts in the field have constantly suggested that systematic intervention should be implemented through a team-based multicomponent approach aimed to reduce the incidence and duration of delirium. Surgery involves many health care workers with different expertise who are not familiar with delirium. For a team-based approach on the management of delirium, it is vital that all medical personnel concerned have a common understanding of delirium and keep in constant communication. Postoperative delirium is a common complication and exerts an enormous burden on patients, their families, hospitals, and public resources. To alleviate this burden, this article aimed to review general features and the latest evidence-based knowledge of delirium with a focus on postoperative delirium.


Asunto(s)
Delirio/terapia , Complicaciones Posoperatorias/terapia , Delirio/diagnóstico , Delirio/etiología , Delirio/prevención & control , Humanos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo
13.
Medicine (Baltimore) ; 97(52): e13912, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30593210

RESUMEN

This study aimed to evaluate the psychological distress and associated risk factors for distress among patients with gastric epithelial neoplasm undergoing endoscopic submucosal dissection (ESD).A total of 91 patients treated with ESD for gastric epithelial neoplasm between May 2015 and June 2016 were prospectively enrolled. Sociodemographic factors, psychological distress, anxiety, depression, stress, and associated risk factors for psychological distress were evaluated the day before ESD.Twenty-six (28.6%) patients were identified as patients with psychological distress. The psychological distress group had a higher female ratio and more depression and anxiety symptoms than the non-distress group. Distress was also related to stress level. A multivariate analysis showed that unmarried status (odds ratio [OR], 4.94; 95% confidence interval [CI], 1.13-21.56, P = .034), anxiety (OR, 1.24; 95% CI, 1.12-1.39, P <.001), and stress (OR, 1.06; 95% CI, 1.01-1.12, P = .011) were associated with psychological distress.An unmarried status and a high level of anxiety and stress were associated with more psychological distress in patients undergoing gastric ESD. It could be helpful to screen and proactively monitor patients with such conditions before performing gastric ESD.


Asunto(s)
Resección Endoscópica de la Mucosa/psicología , Neoplasias Glandulares y Epiteliales/psicología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Gástricas/psicología , Neoplasias Gástricas/cirugía , Estrés Psicológico/epidemiología , Anciano , Ansiedad/epidemiología , Depresión/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores Socioeconómicos , Neoplasias Gástricas/patología
14.
J Crit Care ; 47: 65-69, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29929153

RESUMEN

PURPOSE: Pain and anxiety are understudied despite their importance to the general medical condition. The aim of the present study was to examine the effects of pain and anxiety and their relationship to the doses of opioids and anxiolytics administered in intensive care unit (ICU) patients. METHODS: The subjects included 1349 conscious, critically ill patients admitted to an ICU. Psychiatrists evaluated the patients daily for pain and anxiety. Data regarding the doses of opioids and benzodiazepines administered were gathered. Linear mixed model was used for analysis. RESULTS: The pain and anxiety experienced by patients in the ICU were significantly correlated. Pain had significant main effects on the dose of opioids administered. No significant effects of anxiety on the daily dose of anxiolytics or opioids given were detected. CONCLUSIONS: Due to their closely linked relationship, pain and anxiety, can affect one another, and one can influence the other to appear more severe. In addition, anxiety can be underestimated in ICU patients. The present study suggests the need for precise evaluation and a comprehensive approach to the management of pain and anxiety. In addition, this study implies that management of anxiety may affect pain reduction, given the close correlation between the two.


Asunto(s)
Ansiedad/tratamiento farmacológico , Ansiedad/fisiopatología , Esquema de Medicación , Manejo del Dolor/métodos , Dolor/tratamiento farmacológico , Dolor/fisiopatología , Adulto , Anciano , Algoritmos , Analgésicos Opioides/uso terapéutico , Ansiolíticos/uso terapéutico , Trastornos de Ansiedad , Benzodiazepinas/uso terapéutico , Cuidados Críticos , Enfermedad Crítica , Femenino , Humanos , Unidades de Cuidados Intensivos , Modelos Lineales , Masculino , Persona de Mediana Edad , Admisión del Paciente , Índice de Severidad de la Enfermedad
15.
Acute Crit Care ; 33(1): 23-33, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31723856

RESUMEN

BACKGROUND: Delirium is common among intensive care unit (ICU) patients, so recent clinical guidelines recommended routine delirium monitoring in the ICU. But, its effect on the patient's clinical outcome is still controversial. In particular, the effect of systems that inform the primary physician of the results of monitoring is largely unknown. METHODS: The delirium notification program using bedside signs and electronic chart notifications was applied to the pre-existing delirium monitoring protocol. Every patient was routinely evaluated for delirium, pain, and anxiety using validated tools. Clinical outcomes, including duration of delirium, ICU stay, and mortality were reviewed and compared for 3 months before and after the program implementation. RESULTS: There was no significant difference between the two periods of delirium, ICU stay, and mortality. However, anxiety, an important prognostic factor in the ICU survivor's mental health, was significantly reduced and pain tended to decrease. CONCLUSIONS: Increasing the physician's awareness of the patient's mental state by using a notification program could reduce the anxiety of ICU patients even though it may not reduce delirium. The results suggested that the method of delivering the results of monitoring was also an important factor in the success of the delirium monitoring program.

16.
Int J Med Sci ; 14(6): 515-522, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28638266

RESUMEN

Aims: GS28 (Golgi SNARE protein, 28 kDa), a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) protein family, plays a critical role in mammalian endoplasmic reticulum (ER)-Golgi or intra-Golgi vesicle transport. To date, few researches on the GS28 protein in human cancer tissues have been reported. In this study, we assessed the prognostic value of GS28 in patients with colorectal cancer (CRC). Methods and results: We screened for GS28 expression using immunohistochemistry in 230 surgical CRC specimens. The CRCs were right-sided and left-sided in 28.3% (65/230) and 71.3% (164/230) of patients, respectively. GS28 staining results were available in 214 cases. Among these, there were 26 nuclear predominant cases and 188 non-nuclear predominant cases. Stromal GS28 expression was noted in 152 cases of CRC. GS28 nuclear predominant immunoreactivity was significantly associated with advanced tumour stage (p = 0.045) and marginally associated with perineural invasion (p = 0.064). Decreased GS28 expression in the stromal cells was significantly associated with lymph node metastasis (N stage; p = 0.036). GS28 expression was not associated with epidermal growth factor receptor (EGFR) immunohistochemical positivity or KRAS mutation status. Investigation of the prognostic value of GS28 with Kaplan-Meier analysis revealed a correlation with overall survival (p = 0.004). Cases with GS28 nuclear predominant expression had significantly poorer overall survival than those with a non-nuclear predominant pattern. Conclusions: Taken together, these results indicate that GS28 nuclear predominant expression could serve as a prognostic marker for CRC and may help in identifying aggressive forms of CRC.


Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Pronóstico , Proteínas Qb-SNARE/genética , Adulto , Anciano , Anciano de 80 o más Años , Transporte Biológico/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , Receptores ErbB/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Aparato de Golgi/genética , Aparato de Golgi/metabolismo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia
17.
Clin Colorectal Cancer ; 16(2): e73-e88, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27780749

RESUMEN

BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Proto-Oncogénicas p21(ras)/genética , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor/metabolismo , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Cetuximab/administración & dosificación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Tasa de Supervivencia , Proteínas ras/genética
18.
Int J Radiat Oncol Biol Phys ; 92(3): 540-7, 2015 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-26068489

RESUMEN

OBJECTIVE: To explore the role of adjuvant chemotherapy for patients with ypT0-2N0 rectal cancer treated by preoperative chemoradiation therapy (PCRT) and radical resection. PATIENTS AND METHODS: A national consortium of 10 institutions was formed, and patients with ypT0-2N0 mid- and low-rectal cancer after PCRT and radical resection from 2004 to 2009 were included. Patients were categorized into 2 groups according to receipt of additional adjuvant chemotherapy: Adj CTx (+) versus Adj CTx (-). Propensity scores were calculated and used to perform matched and adjusted analyses comparing relapse-free survival (RFS) between treatment groups while controlling for potential confounding. RESULTS: A total of 1016 patients, who met the selection criteria, were evaluated. Of these, 106 (10.4%) did not receive adjuvant chemotherapy. There was no overall improvement in 5-year RFS as a result of adjuvant chemotherapy [91.6% for Adj CTx (+) vs 87.5% for Adj CTx (-), P=.18]. There were no differences in 5-year local recurrence and distant metastasis rate between the 2 groups. In patients who show moderate, minimal, or no regression in tumor regression grade, however, possible association of adjuvant chemotherapy with RFS would be considered (hazard ratio 0.35; 95% confidence interval 0.14-0.88; P=.03). Cox regression analysis after propensity score matching failed to show that addition of adjuvant chemotherapy was associated with improved RFS (hazard ratio 0.81; 95% confidence interval 0.39-1.70; P=.58). CONCLUSIONS: Adjuvant chemotherapy seemed to not influence the RFS of patients with ypT0-2N0 rectal cancer after PCRT followed by radical resection. Thus, the addition of adjuvant chemotherapy needs to be weighed against its oncologic benefits.


Asunto(s)
Adenocarcinoma/patología , Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia Adyuvante , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Anciano , Canal Anal , Capecitabina , Quimioterapia Adyuvante , Intervalos de Confianza , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tratamientos Conservadores del Órgano , Cuidados Preoperatorios , Puntaje de Propensión , Dosificación Radioterapéutica , Neoplasias del Recto/mortalidad , Neoplasias del Recto/cirugía , Análisis de Regresión , Resultado del Tratamiento
19.
Int J Med Sci ; 12(2): 92-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25589885

RESUMEN

BACKGROUND: Syndecan-1 (SDC1) is reported to modulate several key processes of tumorigenesis and has variable expression in many cancers. To date, the cause of altered expression has not been elucidated. In this study, we compared SDC1 expression with various clinicopathological parameters and molecular markers to evaluate its clinical significance in colorectal carcinoma. METHODS: We screened for SDC1 expression using immunohistochemistry in 230 surgical specimens of primary colorectal carcinoma from patients consecutively treated between 2008 and 2011 at Seoul St. Mary's Hospital, The Catholic University of Korea. The relationship between SDC1 expression and various clinicopathological parameters and molecular markers was analyzed. RESULTS: The tumors were principally located in the left colon (71.3%) and rectum (33.5%). There were 216 (93.9%) adenocarcinomas, 10 (4.3%) mucinous adenocarcinomas, and 4 other tumors. Most of the carcinomas were pT3 (68.3%) and pT4 (22.2%). There was regional lymph node metastasis in 140 patients. SDC1 expression was identified in the cancer cells of 212 (96.8%) colon cancer cases. Of the SDC1-positive cases, 131 showed predominantly membranous immunopositivity, and 81 showed a predominantly cytoplasmic staining pattern. Mixed membranous and cytoplasmic staining was observed in 154 cases. In 93 cases, stromal SDC1 reactivity was noted. Epithelial SDC1 immunopositivity was significantly associated with tumor size (p=0.016) and epidermal growth factor receptor expression (p=0.006). However, it was not significantly correlated with lymph node metastasis, distant metastasis, lymphatic or vascular invasion, or KRAS mutation. In addition, stromal SDC1 immunopositivity was significantly associated with the male sex (p=0.018). CONCLUSIONS: The expression profile of SDC1 may be of clinical value in colorectal cancer and may help in identifying aggressive forms of colorectal carcinoma. Further studies are needed in order to better understand the role of SDC1 in the progression and invasiveness of colorectal carcinoma.


Asunto(s)
Neoplasias Colorrectales/metabolismo , Receptores ErbB/metabolismo , Sindecano-1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/genética , Receptores ErbB/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , Sindecano-1/genética , Análisis de Matrices Tisulares , Proteínas ras/genética , Proteínas ras/metabolismo
20.
Yonsei Med J ; 55(6): 1721-8, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25323912

RESUMEN

PURPOSE: It is well known that expressive language impairment is commonly less severe than receptive language impairment in children with autism spectrum disorder (ASD). However, this result is based on experiments in Western countries with Western language scales. This study tries to find whether the result above is applicable for toddlers in a non-Western country; more specifically, in Korea with non-Western language scales. MATERIALS AND METHODS: The participants were 166 toddlers aged between 20 months and 50 months who visited the clinic from December 2010 to January 2013. The number of toddlers diagnosed as ASD and developmental language delay (DLD) was 103 and 63, respectively. Language development level was assessed using Sequenced Language Scale for Infants (SELSI), a Korean language scale. Using SELSI, each group was divided into 3 sub-groups. Moreover, the group difference by age was observed by dividing them into three age groups. Chi-square test and linear-by-linear association was used for analysis. RESULTS: Receptive language ability of the DLD group was superior to that of the ASD group in all age groups. However, expressive language ability in both groups showed no difference in all age groups. A greater proportion of expressive dominant type was found in ASD. The 20-29 months group in ASD showed the largest proportion of expressive language dominant type in the three age groups, suggesting that the younger the ASD toddler is, the more severe the receptive language impairment is. CONCLUSION: These findings suggest that receptive-expressive language characteristics in ASD at earlier age could be useful in the early detection of ASD.


Asunto(s)
Trastornos Generalizados del Desarrollo Infantil/complicaciones , Discapacidades del Desarrollo/complicaciones , Trastornos del Desarrollo del Lenguaje/diagnóstico , Desarrollo del Lenguaje , Lenguaje , Preescolar , Diagnóstico Precoz , Femenino , Humanos , Lactante , Trastornos del Desarrollo del Lenguaje/complicaciones , Pruebas del Lenguaje , Masculino , República de Corea
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