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1.
Sci Rep ; 14(1): 397, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172246

RESUMEN

This study aimed to examine the impact of the COVID-19 pandemic on the emergency department (ED) visits of cardiovascular disease (CVD) patients. The customized data of the National Health Insurance Service (NHIS) from 2017 to 2020 were analyzed. CVD patients were defined by the code 'V192' based on the NHIS coverage benefit expansion policy. The number of ED visits of CVD patients, as well as executed procedures in 2020 (during the pandemic), were compared to the corresponding average numbers in 2018 and 2019 (prepandemic). Stratification by age group, residential area and hospital location was performed. The number of ED visits of newly diagnosed CVD patients decreased by 2.1% nationwide in 2020 (2018-2019: 97,041; 2020: 95,038) and decreased the most (by 14.1%) in March (2018-2019: 8539; 2020: 7334). However, the number of executed procedures increased by 1.1% nationwide in 2020 (2018-2019: 74,696; 2020: 75,520), while it decreased by 11.9% in April (2018-2019: 6603; 2020: 5819). The most notable decreases in the number of newly diagnosed CVD patients (31.7%) and procedures (29.2%) in March 2020 were observed in the Daegu·Gyeongbuk area. CVD patients living in the epicenter of the COVID-19 pandemic may experience difficulty accessing healthcare facilities and receiving proper treatment.


Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Humanos , COVID-19/epidemiología , Pandemias , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/terapia , Visitas a la Sala de Emergencias , Servicio de Urgencia en Hospital , República de Corea/epidemiología , Estudios Retrospectivos
2.
J Cancer Prev ; 28(2): 47-52, 2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37434794

RESUMEN

Data from the Korean National Health Insurance Service (NHIS) have been widely used to provide real-world evidence. Due to the nature of claims data, researchers use operational definitions to define patients with specific diseases. This study aimed to conduct a systematic review of the operational definitions of liver cancer used in studies based on the NHIS database and to suggest the most appropriate operational definition. Literature search was completed on January 6, 2021, using PubMed and KoreaMed. We applied the most frequently used operational definitions of liver cancer to the NHIS-National Sample Cohort and calculated age-standardized incidence rates (ASRs) of liver cancer by year. The ASRs using each operational definition were compared with the ASR from the Korea Central Cancer (KCCR) data. Among 236 articles, 90 were selected for review, covering histologically various kinds of liver cancer and varied by study subjects. Most studies (n = 79) did not mention whether the codes for the operational definition were from only the main diagnosis or from both the main and sub-diagnosis. The most frequently used operational definition was C22 (n = 39); however, the most similar operational definition was the ASR using "C22.0 or C22.9" for men and "C22.0" for women as the main diagnosis to the ASR from the KCCR. Based on the comparison with KCCR data, we suggest using "C22.0 or C22.9" for men and "C22.0" for women as the main diagnosis for the operational definition of liver cancer when using the NHIS data.

3.
Yonsei Med J ; 64(7): 463-470, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37365741

RESUMEN

PURPOSE: The first year of the COVID-19 pandemic in Korea elicited changes in healthcare service utilization. This study aimed to report changes in healthcare service utilization among cancer patients during the first year of the COVID-19 pandemic in Korea. MATERIALS AND METHODS: We analyzed records from National Health Insurance Service Database and identified cancer patients as those with specific beneficiary codes ("V193" or "V194") assigned to cancer patients. We calculated percentage changes in the number of patients between 2019 and 2020 based on claims records for outpatient clinic visits, hospitalization, and emergency room visits by month, age group, residential areas, and hospital location. RESULTS: The number of newly diagnosed cancer patients in 2020 decreased by 3.2%, compared to the previous year. The number of patients who visited an outpatient clinic, were hospitalized, and visited the emergency room decreased by 2.6%, 4.0%, and 3.5%, respectively, in 2020, compared to the year 2019. CONCLUSION: During the first year of the COVID-19 pandemic, the number of newly diagnosed cancer patients decreased by 3.2%, compared to the previous year, and their utilization of healthcare services declined significantly after the outbreak of COVID-19.


Asunto(s)
COVID-19 , Neoplasias , Humanos , COVID-19/epidemiología , Pandemias , Hospitalización , Servicio de Urgencia en Hospital , Neoplasias/epidemiología , Neoplasias/terapia , Atención a la Salud
4.
Gut Liver ; 17(1): 159-169, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36317517

RESUMEN

Background/Aims: Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. Methods: Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of E-cadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. Results: Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0-2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0-2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). Conclusions: This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Pronóstico , Interleucina-6/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Colangiocarcinoma/cirugía , Neoplasias de los Conductos Biliares/cirugía , Cadherinas/análisis , Cadherinas/metabolismo , Receptores ErbB/análisis , Receptores ErbB/metabolismo , Conductos Biliares Intrahepáticos , Inmunoensayo
5.
Eur J Med Chem ; 246: 114999, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36493620

RESUMEN

Prostate cancer patients primarily receive androgen receptor (AR)-targeted drugs as a primary treatment option because prostate cancer is associated with highly activated AR signaling. AR amplification made prostate cancer cells viable under treatment of AR-targeted therapy, leading to castration resistance. AR amplification was more common in enzalutamide-resistant patients. As a strategy to overcome castration resistance and to improve the efficacy of enzalutamide, second-generation nonsteroidal antiandrogen drugs for castration-resistant prostate cancer (CRPC) including topoisomerase II (topo II) poisons such as etoposide and mitoxantrone, have been administered in combination with enzalutamide. In the present study, it was confirmed that amplification of topo IIα, but not I and IIß, was directly and proportionally associated with poor clinical outcome of Prostate cancer. Among a novel series of newly designed and synthesized 7-(3-aminopropyloxy)-substituted flavone analogues, compound 6, the most potent derivative, was further characterized and identified as a topo IIα catalytic inhibitor that intercalates into DNA and binds to the DNA minor groove with better efficacy and less genotoxicity than etoposide, a topo II poison. Compound 6 showed remarkable efficacy in inhibiting AR-negative CRPC cell growth and sensitizing activity to enzalutamide in AR-positive CRPC cells, thus confirming the potential of topo IIα catalytic inhibitor to overcome resistance to androgen deprivation therapy.


Asunto(s)
Flavonas , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Antagonistas de Andrógenos , Etopósido/uso terapéutico , Resistencia a Antineoplásicos , Receptores Androgénicos/metabolismo , Nitrilos/farmacología , ADN-Topoisomerasas de Tipo II , Flavonas/uso terapéutico
6.
EMBO Rep ; 23(8): e52977, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35695065

RESUMEN

Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers despite a relatively low incidence. Angiogenesis, one of the hallmarks of cancer, is essential for the pathogenesis of EOC, which is related to the induction of angiogenic factors. We found that ELF3 was highly expressed in EOCs under hypoxia and functioned as a transcription factor for IGF1. The ELF3-mediated increase in the secretion of IGF1 and VEGF promoted endothelial cell proliferation, migration, and EOC angiogenesis. Although this situation was much exaggerated under hypoxia, ELF3 silencing under hypoxia significantly attenuated angiogenic activity in endothelial cells by reducing the expression and secretion of IGF1 and VEGF. ELF3 silencing attenuated angiogenesis and tumorigenesis in ex vivo and xenograft mouse models. Consequently, ELF3 plays an important role in the induction of angiogenesis and tumorigenesis in EOC as a transcription factor of IGF1. A detailed understanding of the biological mechanism of ELF3 may both improve current antiangiogenic therapies and have anticancer effects for EOC.


Asunto(s)
Proteínas de Unión al ADN , Neoplasias Ováricas , Proteínas Proto-Oncogénicas c-ets , Factores de Transcripción , Animales , Carcinogénesis/genética , Carcinoma Epitelial de Ovario , Línea Celular Tumoral , Proteínas de Unión al ADN/genética , Células Endoteliales/metabolismo , Femenino , Humanos , Hipoxia , Factor I del Crecimiento Similar a la Insulina/genética , Ratones , Neovascularización Patológica/patología , Neoplasias Ováricas/metabolismo , Proteínas Proto-Oncogénicas c-ets/genética , Receptor IGF Tipo 1/genética , Factores de Transcripción/genética , Factor A de Crecimiento Endotelial Vascular/genética
7.
Epidemiol Health ; 44: e2022053, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35760396

RESUMEN

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has affected the utilization of healthcare services, including participation in cancer screening programs. We compared cancer screening participation rates for colorectal, gastric, breast, and cervical cancers among participants in the National Cancer Screening Program (NCSP) in 2019 and 2020 to address the potential distraction effect of COVID-19 on cancer screening. METHODS: Data from the NCSP for 4 cancer types (stomach, colorectal, breast, and cervical) in 2019 and 2020 were used to calculate cancer screening participation rates by calendar month, gender, age group, and geographical region. Monthly participation rates were analyzed per 1,000 eligible individuals. RESULTS: The screening participation rate decreased in 2020 compared to 2019 for all 4 cancers: colorectal (40.5 vs. 35.3%), gastric (61.9 vs. 54.6%), breast (63.8 vs. 55.8%), and cervical (57.8 vs. 52.2%) cancers. Following 2 major COVID-19 waves in March and December 2020, the participation rates in the 4 types of cancer screening dropped compared with those in 2019. The highest decline was observed in the elderly population aged 80 years and older (percentage change: -21% for colorectal cancer; -20% for gastric cancer; -26% for breast cancer; -20% for cervical cancer). CONCLUSIONS: After the 2 major COVID-19 waves, the screening participation rate for 4 types of cancer declined compared with 2019. Further studies are needed to identify the indirect effects of the COVID-19 pandemic on cancer patients, such as delayed diagnoses of cancer or excess cancer deaths.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Neoplasias Colorrectales , Neoplasias del Cuello Uterino , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , COVID-19/diagnóstico , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Detección Precoz del Cáncer , Femenino , Humanos , Tamizaje Masivo , Pandemias , República de Corea/epidemiología , Estómago , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control
8.
Cancers (Basel) ; 13(13)2021 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-34203272

RESUMEN

Glial cells comprise the non-sensory parts of the central nervous system as well as the peripheral nervous system. Glial cells, also known as neuroglia, constitute a significant portion of the mammalian nervous system and can be viewed simply as a matrix of neural cells. Despite being the "Nervenkitt" or "glue of the nerves", they aptly serve multiple roles, including neuron repair, myelin sheath formation, and cerebrospinal fluid circulation. Ependymal cells are one of four kinds of glial cells that exert distinct functions. Tumorigenesis of a glial cell is termed a glioma, and in the case of an ependymal cell, it is called an ependymoma. Among the various gliomas, an ependymoma in children is one of the more challenging brain tumors to cure. Children are afflicted more severely by ependymal tumors than adults. It has appeared from several surveys that ependymoma comprises approximately six to ten percent of all tumors in children. Presently, the surgical removal of the tumor is considered a standard treatment for ependymomas. It has been conspicuously evident that a combination of irradiation therapy and surgery is much more efficacious in treating ependymomas. The main purpose of this review is to present the importance of both a deep understanding and ongoing research into histopathological features and prognoses of ependymomas to ensure that effective diagnostic methods and treatments can be developed.

9.
Ann Lab Med ; 41(6): 532-539, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34108280

RESUMEN

We report the response process of the Laboratory Analysis Task Force (LATF) for Unknown Disease Outbreaks (UDOs) at the Korea Disease Control and Prevention Agency (KDCA) during January 2020 to coronavirus disease 2019 (COVID-19), which developed as a UDO in Korea. The advanced preparedness offered by the laboratory diagnostic algorithm for UDOs related to respiratory syndromes was critical for the rapid identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enabled us to establish and expand the diagnostic capacity for COVID-19 on a national scale in a timely manner.


Asunto(s)
Prueba de COVID-19/normas , COVID-19/diagnóstico , Laboratorios/normas , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , China/epidemiología , Brotes de Enfermedades , Regulación Gubernamental , Humanos , Neumonía/diagnóstico , Neumonía/epidemiología , Neumonía/virología , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación
10.
J Korean Acad Nurs ; 51(2): 150-161, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33993122

RESUMEN

PURPOSE: This study investigated the incidence of urinary tract infection (UTI) in community-dwelling adults and identified the association between obesity and UTI. METHODS: The participants were 4,926 adults aged over 40 years who had no UTIs at the baseline survey of the Korean Genome Epidemiology Study. Obesity was defined according to the cirtieria of Korean Society for the Study of Obesity using body mass index (BMI) data. UTI was defined as those who had self-reported UTI or had either nitrite, or both leukocytes and blood in the urine dipstick test. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariate Cox proportional hazards regression analysis to identify the association between the obesity and UTI. RESULTS: The incidence proportion of UTI was 5.1%, and the incidence density per 1,000 person-years was 25.5. After controlling general characteristics, people with BMI ≥30.0 kg/m² remained 1.66 times (HR = 1.66, 95% CI = 1.06~2.60; p < .05) more likely to have UTI than those with normal weight. This trend was also present in men or people aged ≥ 60 years. Among women aged ≥ 60 years, people with BMI ≥ 30.0 kg/m² were 1.98 times (HR = 1.98, 95% CI = 1.01~3.86; p < .05) more likely to have UTI than those with normal weight. CONCLUSION: The BMI ≥ 30.0 kg/m² is a risk factor of UTIs in Korean adult men over 40 years and women aged ≥ 60 years. It is necessary to emphasize the importance of obesity management to men or women aged ≥ 60 years, specifically.


Asunto(s)
Obesidad/complicaciones , Infecciones Urinarias/complicaciones , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , República de Corea/epidemiología , Factores de Riesgo , Infecciones Urinarias/epidemiología
11.
Osong Public Health Res Perspect ; 11(5): 280-285, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33117632

RESUMEN

OBJECTIVES: The Korea Centers for Disease Control and Prevention has published "A Guideline for Unknown Disease Outbreaks (UDO)." The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. METHODS: The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. RESULTS: Since September 9th, 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. CONCLUSION: Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

12.
Cancers (Basel) ; 12(6)2020 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-32545363

RESUMEN

Trastuzumab (TZMB) is widely used as first line therapy for breast cancer (BC) patients overexpressing human epidermal growth factor receptor 2 (HER2). Despite its clinical benefits, many patients suffer from primary or secondary resistance to this drug within one year. As diverse molecular mechanisms occur contemporaneously during the resistance development, we focused on elucidating the role of heat shock protein 27 (HSP27) in TZMB-resistance, as this protein simultaneously regulates the function of diverse client molecules that are involved in the resistance mechanism. By extensively utilizing TZMB-refractory breast cancer cell lines transduced with diverse phosphovariants of HSP27, our study newly revealed that specific phosphorylation of HSP27 at S15 promoted its S78 phosphorylation and served as key mediator to promote direct interactions that increase the stability of HER2 and protein kinase B (AKT). This phosphorylation promoted nuclear translocation of HER2, enhancing the distinct nuclear function of HER2 that promoted AKT activation and cyclin D1 expression. Co-administration of TZMB and a functional inhibitor of HSP27, J2, significantly reduced the S15/78 phosphorylation of HSP27, which downregulated HER2 and its downstream signals, sensitizing TZMB-refractory cell, and JIMT1-xenograft mouse models to TZMB. Collectively, p-HSP27S15 could serve as a valuable predictive marker and also a therapeutic target for TZMB-resistance.

13.
Cell Host Microbe ; 27(3): 345-357.e6, 2020 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-32078802

RESUMEN

Although the gut microbiome is generally symbiotic or commensal, some microbiome members become pathogenic under certain circumstances. However, the factors driving this pathogenic switch are largely unknown. Pathogenic bacteria can generate uracil that triggers host dual oxidase (DUOX) to produce antimicrobial reactive oxygen species (ROS). We show that pathogens generate uracil and ribose upon nucleoside catabolism of gut luminal uridine, which triggers not only host defenses but also inter-bacterial communication and pathogenesis in Drosophila. Uridine-derived uracil triggers DUOX-dependent ROS generation, whereas ribose induces bacterial quorum sensing (QS) and virulence gene expression. Genes implicated in nucleotide metabolism are found in pathogens but not commensal bacteria, and their genetic ablation blocks QS and the commensal-to-pathogen transition in vivo. Furthermore, commensal bacteria lack functional nucleoside catabolism, which is required to achieve gut-microbe symbiosis, but can become pathogenic by enabling nucleotide catabolism. These findings reveal molecular mechanisms governing the commensal-to-pathogen transition in different contexts of host-microbe interactions.


Asunto(s)
Bacterias/metabolismo , Bacterias/patogenicidad , Drosophila/microbiología , Percepción de Quorum , Uracilo/metabolismo , Virulencia , Animales , Proteínas Bacterianas/metabolismo , Oxidasas Duales/metabolismo , N-Glicosil Hidrolasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ribosa/metabolismo , Simbiosis , Uridina/metabolismo
14.
Bioorg Med Chem ; 26(8): 1909-1919, 2018 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-29510948

RESUMEN

As part of our effort to develop potential topoisomerase IIα (topo IIα) targeting anticancer agents, we systematically designed a new series of hydroxy and chloro-substituted 2,4-diphenyl 5H-chromeno[4,3-b]pyridines. Total eighteen compounds were synthesized and tested for their ability to inhibit the function of topo I and IIα, and proliferation of human breast (T47D), colorectal (HCT15), and cervix (HeLa) cancer cells. Except compound 11, all of the tested compounds displayed selective topo IIα inhibitory activity. Compounds 8-18, 22, 24, and 25 showed excellent topo IIα inhibitory activity than a positive control, etoposide. Most of the compounds appeared to be superior to reference compounds in their antiproliferative activity. Structure-activity relationship (SAR) study has shown that it is better to place the hydroxyphenyl group at the 4-position of the central pyridine for superior topo IIα inhibition and antiproliferative activity. Similarly, the 3'-, or 4'-hydroxyphenyl substitution at the 2- and 4-positon of pyridine ring is important for better activity than 2'-substitution.


Asunto(s)
Antineoplásicos/síntesis química , ADN-Topoisomerasas de Tipo II/metabolismo , Piridinas/química , Inhibidores de Topoisomerasa II/síntesis química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Benzopiranos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN-Topoisomerasas de Tipo II/química , Células HeLa , Humanos , Unión Proteica , Piridinas/metabolismo , Piridinas/farmacología , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/metabolismo , Inhibidores de Topoisomerasa II/farmacología
15.
BMC Cancer ; 16(1): 900, 2016 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-27863481

RESUMEN

BACKGROUND: Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. METHODS: Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. RESULTS: PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (<3.5 g/dL), and 66.2% had NRI score less than 97.5 indicating moderate to severe malnutrition. Hematological adverse events were present in 94% (≥grade 1) and 16.2% (≥grade 3). Non-hematological adverse events occurred in 95.7% (≥grade1) and 16.7% (≥grade 3) of the patients. PG-SGA and NRI score was not associated with treatment-induced adverse events. Multivariate analyses indicated that female, low body mass index, and hypoalbuminemia were independent risk factors for grade 3/4 hematological adverse events. Age was an independent risk factor for grade 3/4 non-hematological adverse events. Neutropenia was the most frequently occurring adverse event, and associated risk factors were female, total gastrectomy, and hypoalbuminemia. CONCLUSIONS: Hypoalbuminemia, not PG-SGA or NRI may predict chemotherapy-induced adverse events in gastrectomized cancer patients.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Evaluación Nutricional , Estado Nutricional , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Índice de Masa Corporal , Estreñimiento/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Neutropenia Febril/etiología , Femenino , Gastrectomía/efectos adversos , Gastrectomía/métodos , Humanos , Hipoalbuminemia/complicaciones , Modelos Logísticos , Masculino , Desnutrición/complicaciones , Persona de Mediana Edad , Análisis Multivariante , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Neoplasias Gástricas/cirugía , Vómitos/etiología
16.
Oncol Rep ; 35(2): 1041-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26555156

RESUMEN

Myristoylated alanine-rich C kinase substrate-like 1 (MARCKSL1) plays a pivotal role in the regulation of apoptosis and has been shown to maintain antitumor and metastasis-suppressive properties. In the present study, we examined the effects of MARCKSL1 as a novel anti-angiogenic agent on the inhibition of angiogenesis-mediated cell migration. MARCKSL1 also reduced vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation, as well as capillary-like tubular structure formation in vitro. MARCKSL1 disrupted phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) in ovarian tumorigenesis. In addition, MARCKSL1 showed potent anti-angiogenic activity and reduced the levels of VEGF and hypoxia-inducible factor 1α (HIF-1α) expression, an essential regulator of angiogenesis. Consistently, MARCKSL1 decreased VEGF­induced phosphorylation of the PI3K/Akt signaling pathway components, including phosphoinositide-dependent protein kinase 1 (PDK-1), mammalian target of rapamycin (mTOR), tuberous sclerosis complex 2 (TSC-2), p70 ribosomal protein S6 kinase (p70S6K), and glycogen synthase kinase 3ß (GSK-3ß) protein. Collectively, our results provide evidence for the physiological/biological function of an endothelial cell system involved in angiogenesis through suppression of Akt/PDK-1/mTOR phosphorylation by interaction with VEGFR-2.


Asunto(s)
Células Endoteliales/fisiología , Proteínas de la Membrana/fisiología , Proteínas de Neoplasias/antagonistas & inhibidores , Neovascularización Patológica/fisiopatología , Procesamiento Proteico-Postraduccional/fisiología , Transducción de Señal/fisiología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Proteínas de Unión a Calmodulina , Línea Celular Tumoral , Movimiento Celular , Femenino , Glucógeno Sintasa Quinasa 3/biosíntesis , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Células Endoteliales de la Vena Umbilical Humana , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteínas de la Membrana/genética , Proteínas de Microfilamentos , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Neoplasias Ováricas/patología , Fosforilación/fisiología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/biosíntesis , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Transfección , Proteína 2 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genética , Técnicas del Sistema de Dos Híbridos
17.
Int Immunopharmacol ; 29(2): 246-253, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26590114

RESUMEN

Oxidative skin damage and skin inflammation play key roles in the pathogenesis of skin-related diseases. Fisetin is a naturally occurring flavonoid abundantly found in several vegetables and fruits. Fisetin has been shown to exert various positive biological effects, such as anti-cancer, anti-proliferative, neuroprotective and anti-oxidative effects. In this study, we investigate the skin protective effects and anti-inflammatory properties of fisetin in hydrogen peroxide- and TNF-α-challenged human keratinocyte HaCaT cells. When HaCaT cells were treated with non-cytotoxic concentrations of fisetin (1-20µM), heme oxygenase (HO)-1 mRNA and protein expression increased in a dose-dependent manner. Furthermore, fisetin dose-dependently increased cell viability and reduced ROS production in hydrogen peroxide-treated HaCaT cells. Fisetin also inhibited the production of NO, PGE2 IL-1ß, IL-6, expression of iNOS and COX-2, and activation of NF-κB in HaCaT cells treated with TNF-α. Fisetin induced Nrf2 translocation to the nuclei. HO-1 siRNA transient transfection reversed the effects of fisetin on cytoprotection, ROS reduction, NO, PGE2, IL-1ß, IL-6, and TNF-α production, and NF-κB DNA-binding activity. Moreover, fisetin increased Akt phosphorylation and a PI3K pathway inhibitor (LY294002) abolished fisetin-induced cytoprotection and NO inhibition. Taken together, these results provide evidence for a beneficial role of fisetin in skin therapy.


Asunto(s)
Antioxidantes/farmacología , Flavonoides/farmacología , Hemo-Oxigenasa 1/biosíntesis , Peróxido de Hidrógeno/antagonistas & inhibidores , Inflamación/prevención & control , Queratinocitos/efectos de los fármacos , Oxidantes/toxicidad , Estrés Oxidativo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Flavonoles , Hemo-Oxigenasa 1/genética , Humanos , Peróxido de Hidrógeno/toxicidad , Inflamación/inducido químicamente , Factor 2 Relacionado con NF-E2/metabolismo , Proteína Oncogénica v-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Factor de Necrosis Tumoral alfa/toxicidad
18.
Oncotarget ; 6(31): 31830-43, 2015 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-26378810

RESUMEN

The suppressor of MEK null (sMEK1) protein possesses pro-apoptotic activities. In the current study, we reveal that sMEK1 functions as a novel anti-angiogenic factor by suppressing vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and capillary-like tubular structure in vitro. In addition, sMEK1 inhibited the phosphorylation of the signaling components up- and downstream of Akt, including phospholipase Cγ1 (PLC-γ1), 3-phosphoinositide-dependent protein kinase 1 (PDK1), endothelial nitric oxide synthetase (eNOS), and hypoxia-inducible factor 1 (HIF-1α) during ovarian tumor progression via binding with vascular endothelial growth factor receptor 2 (VEGFR-2). Furthermore, sMEK1 decreased tumor vascularity and inhibited tumor growth in a xenograft human ovarian tumor model. These results supply convincing evidence that sMEK1 controls endothelial cell function and subsequent angiogenesis by suppressing VEGFR-2-mediated PI3K/Akt/eNOS signaling pathway. Taken together, our results clearly suggest that sMEK1 might be a novel anti-angiogenic and anti-tumor agent for use in ovarian tumor.


Asunto(s)
Proliferación Celular , Células Endoteliales de la Vena Umbilical Humana/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Neoplasias Ováricas/patología , Fosfoproteínas Fosfatasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Apoptosis , Western Blotting , Movimiento Celular , Células Cultivadas , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Técnicas para Inmunoenzimas , Inmunoprecipitación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica , Neoplasias Ováricas/metabolismo , Fosforilación , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Cell Signal ; 27(11): 2150-9, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26278164

RESUMEN

In this study, we investigated a possible mechanism of ß2-microglobulin (ß2M) function in cancer metastases in vitro, using a human ovarian carcinoma cell line. ß2M, a modulator acts as a cell growth-promoting and cellular signaling factors, was identified as a dickkopf-3 (DKK-3) interacting protein. We also observed that DKK-3 suppresses endothelial cell angiogenesis of ß2M through vascular endothelial growth factor receptor-2 (VEGFR-2) in tumorigenesis. Luciferase activity was remarkably reduced by the transfection of DKK-3 in a dose-dependent manner. In addition, over-expression of ß2M activates cell growth by suppressing DKK-3-induced apoptosis. The effect of ß2M on cell cycle and apoptosis-regulatory components was also confirmed through the silencing of ß2M expression. Furthermore, induction of ß2M-mediated VEGFR-2/Akt/mTOR phosphorylation and tumor angiogenesis was significantly suppressed by over-expression of DKK-3. Taken together, our results suggest an underlying mechanism for an increase of ß2M-related activity in ovarian tumor cells.


Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Ováricas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Microglobulina beta-2/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Apoptosis/genética , Apoptosis/fisiología , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica/patología , Quimiocinas , Femenino , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Luciferasas/metabolismo , Metástasis de la Neoplasia/patología , Neovascularización Patológica/patología , Fosforilación , Interferencia de ARN , ARN Interferente Pequeño , Transducción de Señal/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Microglobulina beta-2/genética
20.
Int Immunopharmacol ; 26(1): 194-202, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25843255

RESUMEN

Guggulsterone (GS), a plant steroid and a compound found at high levels in Commiphora myrrha, exhibits anti-inflammatory, anti-cancer, and cholesterol-lowering effects. However, the potential of GS to ameliorate acute pancreatitis (AP) is unknown. The aim of this study was to evaluate the effects of GS on cerulein-induced AP. AP was induced by intraperitoneally injecting supramaximal concentrations of the stable cholecystokinin analog cerulein (50 µg/kg) hourly for 6 h. In the GS-treated group, GS was administered intraperitoneally (10, 25, or 50mg/kg) 1 h before the first cerulein injection. Mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to measure serum lipase levels and evaluate cytokine production. The pancreas and lung were rapidly removed for morphologic and histological examinations, flow cytometry analysis, myeloperoxidase (MPO) assay, and real-time reverse transcription-polymerase chain reaction analysis. Pre-treatment with GS attenuated cerulein-induced histological damage, reduced pancreas weight/body weight ratio, decreased serum lipase levels, inhibited infiltrations of macrophages and neutrophils, and suppressed cytokine production. Additionally, GS treatment suppressed the activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) in the pancreas in cerulein-induced pancreatitis. In conclusion, our results suggest that GS attenuates AP via deactivation of ERK and JNK.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ceruletida/farmacología , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Proteínas Quinasas JNK Activadas por Mitógenos/antagonistas & inhibidores , Pancreatitis/tratamiento farmacológico , Pregnenodionas/uso terapéutico , Enfermedad Aguda , Animales , Antiinflamatorios/administración & dosificación , Western Blotting , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Inyecciones Intraperitoneales , Lipasa/sangre , Ratones Endogámicos C57BL , Páncreas/efectos de los fármacos , Páncreas/inmunología , Páncreas/patología , Pancreatitis/enzimología , Pancreatitis/inmunología , Pregnenodionas/administración & dosificación
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