Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445110

RESUMO

Epidermal growth factor receptor (EGFR) is overexpressed in lung cancer patients. Despite treatment with various EGFR tyrosine kinase inhibitors, recurrence and metastasis of lung cancer are inevitable. Docetaxel (DTX) is an effective conventional drug that is used to treat various cancers. Several researchers have studied the use of traditional herbal medicine in combination with docetaxel, to improve lung cancer treatment. SH003, a novel herbal mixture, exerts anticancer effects in different cancer cell types. Here, we aimed to investigate the apoptotic and anticancer effects of SH003 in combination with DTX, in human non-small-cell lung cancer (NSCLC). SH003, with DTX, induced apoptotic cell death, with increased expression of cleaved caspases and cleaved poly (ADP-ribose) polymerase in NSCLC cells. Moreover, SH003 and DTX induced the apoptosis of H460 cells via the suppression of the EGFR and signal transducer and activator of transcription 3 (STAT3) signaling pathways. In H460 tumor xenograft models, the administration of SH003 or docetaxel alone diminished tumor growth, and their combination effectively killed cancer cells, with increased expression of apoptotic markers and decreased expression of p-EGFR and p-STAT3. Collectively, the combination of SH003 and DTX may be a novel anticancer strategy to overcome the challenges that are associated with conventional lung cancer therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Docetaxel/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fator de Transcrição STAT3/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
2.
Mol Oncol ; 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33931944

RESUMO

Targeting autophagy is a promising therapeutic approach in cancer therapy. Here, we screened 30 traditional herbal medicines to identify novel autophagy regulators and found that Platycodon grandiflorus (PG) and platycodin D (PD), a triterpenoid saponin from PG, inhibited autophagy in glioblastoma multiforme (GBM) cells. Mechanistically, PD prevented lysosomal degradation and the fusion between autophagosomes and lysosomes by inducing sequestration of free cholesterol in lysosomes. The autophagy inhibitory effect of PD was mimicked by both genetic and pharmacological inhibition of Niemann-Pick C1 (NPC1), which exports low-density lipoprotein (LDL)-derived cholesterol from lysosomes. Moreover, PD promoted the uptake of exogenous LDL cholesterol via upregulation of LDL receptor (LDLR), leading to further accumulation of cholesterol within lysosomes and GBM cell death. Importantly, these phenomena were more pronounced in LDLR-overexpressing GBM cells than in normal astrocytes. Finally, blockade of cholesterol uptake by LDLR knockdown reversed the PD-induced inhibition of autophagy and GBM cell growth. Our study proposes that PD could be a potent anti-GBM drug by disrupting cholesterol trafficking and autophagy.

3.
Am J Chin Med ; 49(3): 767-784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33657989

RESUMO

Gliomas are the mostly observed form of primary brain tumor, and glioblastoma multiforme (GBM) shows the highest incidence. The survival rate of GBM is fairly poor; thus, discovery of effective treatment options is required. Among several suggested targets for therapy, the Axl/IL-6/STAT3 signaling pathway has gained recent interest because of its important role within cancer microenvironment. Quercetin, a plant flavonoid, is well known for its anticancer action. However, the effect of quercetin on Axl has never been reported. Quercetin treatment significantly reduced cell viability in two GBM cell lines of U87MG and U373MG while keeping 85% of normal astrocytes alive. Further western blot assays suggested that quercetin induces apoptosis but does not affect Akt or mitogen-activated protein kinases, factors related to cell proliferation. Quercetin also decreased IL-6 release and phosphorylation of STAT3 in GBM cells. In addition, gene expression, protein expression, and half-life of synthesized Axl protein were all suppressed by quercetin. By applying shRNA for knockdown of Axl, we could confirm that the role of Axl was crucial in the apoptotic effect of quercetin on GBM cells. In conclusion, we suggest quercetin as a potential anticancer agent, which may improve cancer microenvironment of GBM via the Axl/IL-6/STAT3 pathway.


Assuntos
Antineoplásicos Fitogênicos , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Interleucina-6/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Quercetina/farmacologia , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/genética , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Humanos , Fitoterapia , Quercetina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética
4.
Echocardiography ; 38(2): 175-182, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33406280

RESUMO

INTRODUCTION: Long-term right ventricular pacing is the only treatment for patients with a complete atrioventricular block (CAVB); however, it frequently triggers ventricular dys-synchrony with left ventricular (LV) dysfunction. Previous studies showed that an early decline of LV global longitudinal strain (GLS) predicts pacing-induced LV dysfunction. We aimed to investigate the potential ability of the initial LV strain to predict pacing-induced cardiomyopathy (PICM) through long-term follow-ups. METHODS: We retrospectively enrolled 80 patients with CAVB with normal LV function who were implanted with dual-chamber pacemakers between 2008 and 2018. Echocardiographic data and parameters (including longitudinal, radial, and circumferential strain based on speckle-tracking) were analyzed for the pre-implant (≤6 months) and post-implant periods. PICM was defined as a ≥10% reduction in the left ventricular ejection fraction (LVEF) resulting in an LVEF of <50% during the post-implant period. Predictors of PICM were identified using Cox proportional hazard models. RESULTS: Patients who developed PICM were more likely to exhibit lower baseline LV GLS, as well as wider native and pacing QRS durations, than those who did not develop PICM (P = .016, P = .011, and P = .026, respectively). In the multivariate analysis, pre-implant LV GLS (hazard ratio: 1.27; 95% confidence interval 1.009-1.492; P = .004) was independently associated with the development of PICM. CONCLUSION: A lower baseline LV GLS predicts an increased risk of PICM. Patients with CAVB exhibiting low GLS are at increased risk of PICM. More frequent follow-up visits are warranted in these patients, who may also require de novo His-bundle pacing or an upgrade to biventricular pacing.


Assuntos
Bloqueio Atrioventricular , Cardiomiopatias , Bloqueio Atrioventricular/terapia , Cardiomiopatias/complicações , Cardiomiopatias/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
5.
Sci Rep ; 10(1): 19834, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199761

RESUMO

The root of Platycodon grandiflorum (PG) has long been used as a traditional herbal medicine in Asian country. Platycondin D (PD), triterpenoid saponin that is a main constituent of PG, exhibits various biological activities such as anti-inflammatory, anti-oxidant, anti-diabetic, and anti-cancer effects. A previous study showed that PD had cholesterol-lowering effects in mice that develop hypercholesterolemia, but the underlying molecular mechanisms have not been elucidated during the last decade. Here, we demonstrated that both PG and PD markedly increased levels of cell surface low-density lipoprotein receptor (LDLR) by down-regulation of the E3 ubiquitin ligase named inducible degrader of the LDLR (IDOL) mRNA, leading to the enhanced uptake of LDL-derived cholesterol (LDL-C) in hepatic cells. Furthermore, cycloheximide chase analysis and in vivo ubiquitination assay revealed that PD increased the half-life of LDLR protein by reducing IDOL-mediated LDLR ubiquitination. Finally, we demonstrated that treatment of HepG2 cells with simvastatin in combination with PG and PD had synergistic effects on the improvement of LDLR expression and LDL-C uptake. Together, these results provide the first molecular evidence for anti-hypercholesterolemic activity of PD and suggest that PD alone or together with statin could be a potential therapeutic option in the treatment of atherosclerotic cardiovascular disease.


Assuntos
LDL-Colesterol/metabolismo , Hepatócitos/metabolismo , Platycodon/química , Receptores de LDL/metabolismo , Saponinas/farmacologia , Triterpenos/farmacologia , Ubiquitina-Proteína Ligases/genética , Linhagem Celular , Cicloeximida/farmacologia , Sinergismo Farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Meia-Vida , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Humanos , Raízes de Plantas/química , Sinvastatina/farmacologia , Ubiquitinação
6.
Artigo em Inglês | MEDLINE | ID: mdl-33029168

RESUMO

Pancreatic cancer has a poor prognosis with a five-year survival rate of less than 10%. Moreover, chemotherapy is mostly rendered ineffective owing to chemotherapy resistance and cytotoxicity. Therefore, the development of effective therapeutic strategies and novel drugs against pancreatic cancer is an urgent need. Cucurbitacin D (CuD), a plant steroid derived from Trichosanthes kirilowii, is an anticancer agent effective against various cancer cell lines. However, the anticancer activity and molecular mechanism of CuD in pancreatic cancer remain unknown. Therefore, we aimed to investigate the anticancer activity and molecular mechanism of CuD in the human pancreatic cancer cell line, Capan-1. CuD induced cell cycle arrest at the G2/M phase, apoptosis, and reactive oxygen species generation in Capan-1 cell line. In addition, CuD induced the activation of the p38 MAPK signaling pathway that regulates apoptosis, which was also inhibited by N-acetyl-L-cysteine and the p38 inhibitor SB203580. These data suggest that CuD induces cell cycle arrest and apoptosis via the ROS/p38 pathway in Capan-1 pancreatic cancer cell line; hence, CuD is a promising candidate that should be explored further for its effectiveness as an anticancer agent against pancreatic cancer.

7.
J Hypertens ; 38(3): 527-535, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31693535

RESUMO

OBJECTIVE: The efficacy and safety of nebivolol in patients with hypertension is well established, but its effect in Asian patients with essential hypertension in the real world has not been studied. METHODS: Adult South Korean patients with essential hypertension, with or without comorbidities, were enrolled to participate in this prospective, single-arm, open, observational study; 3011 patients received nebivolol either as monotherapy or add-on therapy. Changes in SBP, DBP and heart rate (HR) at 12 and 24 weeks were evaluated. Subgroup analysis for BP changes in newly diagnosed (de novo) patients and those receiving other antihypertensives at study entry were also conducted. RESULTS: Nebivolol significantly decreased mean SBP and DBP at 12 and 24 weeks compared with baseline (P < 0.0001). A significant reduction in HR was also observed at 12 and 24 weeks (P < 0.0001). The reductions of SBP and DBP were notably greater when nebivolol was used as monotherapy in de novo patients (P < 0.0001) and as add-on therapy to existing antihypertensives (angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors and calcium channel blockers; P < 0.0001). Majority of the reported adverse events were mild; the most common adverse events were dizziness (1.3%), headache (1.0%) and dyspnea (0.9%). CONCLUSION: Despite the limitations associated with observational studies, this real-world study in Asian patients with essential hypertension with and without comorbidities, demonstrated the efficacy and safety of once daily nebivolol, either as monotherapy or add-on therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT03847350.SDC Callout: Video Abstract, http://links.lww.com/HJH/B172.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Nebivolol/uso terapêutico , Humanos , Estudos Prospectivos , República da Coreia
8.
Clin Cardiol ; 42(12): 1210-1221, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580531

RESUMO

BACKGROUND: Scrub typhus is a well-known infectious disorder of the Asia-Pacific region. However, adverse cardiac outcomes are an under-recognized complication of scrub typhus infection, and new-onset AF has been reported to be a prognostic factor in other, more common infectious diseases. The present study investigated whether new-onset atrial fibrillation (AF) is significantly associated with 3-month mortality and adverse cardiac complications in scrub typhus infection. METHODS: We examined data from the National Health Information Database (NHID) which covers nearly the entire population of South Korea, from 2006 to 2016. In total, 233 473 patients diagnosed with scrub typhus infection were selected as study participants. New-onset AF, acute heart failure (AHF), ischemic heart disease (IHD), and 3-month mortality were analyzed using a generalized estimating equation model with a Poisson distribution. RESULTS: Of these, 2402 patients (1%) were diagnosed with new-onset AF (87.2% were over 60 years of age, 43.3% were male). Those with new-onset AF were more likely to have underlying cardiovascular disease compared to those without new-onset AF. After being adjusted for demographic factors and comorbidities, those with new-onset AF had a higher incidence risk of concurrent AHF (4.1-fold) and IHD (1.9-fold) compared with those without new-onset AF. In particular, the 3-month mortality was also significantly associated with new-onset AF (1.3-fold), concurrent AHF (2.4-fold), and IHD (13.7-fold). CONCLUSIONS: New-onset AF was significantly associated with 3-month mortality and concurrent AHF and IHD. Therefore, new-onset AF could be a poor prognostic factor for 3-month mortality and cardiac complications in scrub typhus infection.


Assuntos
Fibrilação Atrial/epidemiologia , Tifo por Ácaros/complicações , Tifo por Ácaros/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-31191706

RESUMO

Dysregulated lipid metabolism is a prominent feature of prostate cancers (PCas); several enzymes involved in lipid accumulation are highly expressed. Here, we elucidated efficacy of TJ001, a traditional herbal decoction, in inhibiting de novo lipogenesis. TJ001 had significant cytotoxicity against DU145 but not PC3 and LNCaP cells and, similarly, TJ001 markedly AMPK phosphorylation only in DU145 cells. This was accompanied by the downregulation of phosphorylated-acetyl coenzyme A carboxylase (ACC) expression and sterol regulatory element-binding protein 1 (SREBP1) proteolytic cleavage, thereby inhibiting its role as a transcription factor to induce lipid biosynthesis. When Oil Red O staining was performed, it is reflected in the reduction of lipid droplets (LDs). TJ001 also induced G1/S cell cycle arrest via a cell cycle inhibitor (CKI) p21WAF1/CIP1 upregulation. Although p53 proteins remained unchanged, both cyclin E and cyclin D1 were decreased. Moreover, TJ001 suppressed the mammalian target of rapamycin (mTOR) signaling pathway. Generally, the prolonged G1/S phase arrest accompanies apoptosis, but TJ001 failed to work as a trigger apoptosis in DU145 cells. We showed that mutant p53 proteins were required for the survival of DU145 cells. In presence of TJ001, inhibition of endogenous mutant p53 by RNAi led to cell viability reduction and induction of the p-AMPK/AMPK ratio. In addition, it induced apoptotic cell death in DU145 cells. At the cellular level, induction of PARP, caspase-3, and caspase-9 cleavages was observed, and caspase-3 activity was increased in the p53 knockdown cells treated with TJ001. Taken together, we demonstrated that TJ001 inhibited cell growth in DU145 prostate cancer cells as indicated by blocking lipogenesis and induction in G1/S cell cycle arrest. In addition, we may provide an evidence that mutant p53 protein has potential role as an oncogenic action in DU145 cells. Collectively, the combination of mutant p53 targeting and TJ001 treatment resulted in decreased cell growth in DU145 cells.

10.
Catheter Cardiovasc Interv ; 94(3): 378-384, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30604498

RESUMO

OBJECTIVES: We aimed to investigate specific subgroups in which the benefit of transradial coronary interventions (TRIs) would be enhanced. BACKGROUND: The advantage of TRIs over transfemoral coronary interventions (TFIs) might differ according to a given clinical condition, urgency of the procedure, and operator volume pattern. METHODS: Using a cohort from the 2014 Korean Percutaneous Coronary Intervention Registry, in-hospital outcomes of the TRI group (n = 22,993) were matched to those of the TFI group (n = 15,581). After propensity score matching, the composite endpoints between the groups and subgroups for all-cause death, nonfatal myocardial infarctions (MIs), or transfusions were analyzed. RESULTS: The composite endpoints occurred less frequently in the TRI group than the TFI group [2.1% vs. 5.5%, OR 0.63, 95% CI 0.55-0.72]. The TRI group had a lower rate of death (OR 0.44, 95% CI 0.33-0.60) and nonfatal MI (OR 0.66, 95% CI 0.54-0.81) than the TFI group. The TRI group required fewer transfusions than the TFI group (OR 0.72, 95% CI 0.59-0.88). TRI benefits were consistent across subgroups except patients with chronic kidney disease and those treated in low tertile PCI volume centers. The favorable outcome of TRI was greater in the elderly (≥75 years), patients with ST-elevation MI, those who underwent emergent PCI, and those treated in high tertile PCI volume hospitals (P for the interaction <0.001 for all). CONCLUSIONS: Compared to TFI, TRI had favorable composite in-hospital outcomes. TRI benefits were pronounced in high-risk clinical settings and in high PCI volume centers.


Assuntos
Cateterismo Periférico , Doença da Artéria Coronariana/terapia , Artéria Femoral , Intervenção Coronária Percutânea , Artéria Radial , Idoso , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Punções , Sistema de Registros , República da Coreia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Adv Biosyst ; 3(7): e1900013, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-32648670

RESUMO

RNA biomarkers have been recently reported to be associated tightly with the diagnosis and prognosis of many diseases. Particularly, cancers considered to be a serious threat to primates are known to be vastly dominated by genetic networks where RNA plays a key role. RNAs are thus recognized as a major target group that can be used for numerous cancer treatments and it is still required to identify and enumerate them in an effective manner. Here, a new topological transformation-based nanobarcoding technique (TNT) is first reported using fluorescence-DNA barcodes engaged with graphene oxide (GOx ) for effectively discriminating short RNAs such as miRNAs and their single nucleotide polyporphisms in tissue and plasma. Through topological transformation into 3D DNA-RNA polygonal structures, various kinds of microRNAs have been read at the same time and analyzed quantitatively. Also, it positively discerned epidermal growth factor receptor (EGFR) mutations known as single base variations of typical lung cancer specific RNAs. A single variant of 0.785% in target EGFR mutations is explicitly detected. It is speculated that the TNT may be a versatile method for polymerase chain reaction (PCR)-free practical diagnosis of several clinical genetic deviations such as significant biotic RNA and genic fragments and would be a promising alternative to conventional PCR terrains.


Assuntos
Código de Barras de DNA Taxonômico , Grafite , MicroRNAs/genética , Mutação , Polimorfismo de Nucleotídeo Único , Receptores ErbB/genética , Humanos
12.
Korean J Fam Med ; 40(3): 159-164, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30466203

RESUMO

BACKGROUND: This study aimed to investigate the association between physical fitness and cardiometabolic health of Korean children and adolescents. METHODS: In total, 168 participants (89 boys and 79 girls) aged 10-16 years were recruited for the Intervention for Childhood and Adolescent Obesity via Activity and Nutrition Study in 2016. The subjects were categorized into two groups using the definition of metabolic syndrome by the International Diabetes Federation: metabolically unhealthy (with at least two of the five criteria) and healthy groups (with less than one criterion). Correlation analysis of the participants' general characteristics was performed. Odds ratios (ORs) of physical fitness for cardiometabolic risk were evaluated via logistic regression. RESULTS: Metabolically unhealthy children showed greater weight, height, and body mass index, higher Children's Depression Inventory score, and longer screen time than did the metabolically healthy children. Metabolically healthy children showed greater upper and lower extremity muscular strength than did the metabolically unhealthy children (P=0.04 and P<0.001, respectively). In the multiple logistic regression analysis, lower extremity muscle strength was inversely related to the clustered cardiometabolic risk of the children and adolescents with or without adjustment for confounders (OR, 4.32; 95% confidence interval [CI], 1.87-9.97; OR, 7.64; 95% CI, 1.55- 37.74, respectively). CONCLUSION: Physical fitness, especially lower extremity muscle strength, is significantly inversely associated with individual and clustered cardiometabolic risks in Korean children and adolescents.

13.
Korean J Intern Med ; 34(2): 315-323, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29240992

RESUMO

BACKGROUND/AIMS: The induction and recurrence of syncope is a concerning situation that could be unpredicted in the vasovagal syncope (VVS). We investigated a simple predictor for the induced and recurrent VVS during Head-Up table-tilt Test (HUT) and clinically follow-up. METHODS: The 143 consecutive patients with VVS (age 31 ± 19 years, 33 male) who referred by a cardiologist or neurologist and had undergone an echocardiogram, HUT, and a treadmill exercise test (TMT) were recruited and clinically follow-up. Patients were divided into two groups based on the result of HUT and TMT. The data was analyzed and compared between VVS patients and control 141 patients without VVS who were enrolled in the same study period (age 40 ± 5 years, 117 male). RESULTS: The heart rate recovery (HRR), recovery systolic blood pressure (RecSBP), recovery diastolic blood pressure (RecDBP), HRR/RecSBP and HRR/RecDBP were significantly different between controls and VVS during the TMT. Within VVS, even if, baseline characteristics were similar between negative and positive HUT (n = 92 vs. n = 51). HRR (31 ± 10 vs. 35 ± 10), HRR/RecSBP (0.24 ± 0.09 vs. 0.28 ± 0.09) and HRR/RecDBP (0.49 ± 0.18 vs. 0.58 ± 0.19) were significantly different between negative and positive HUT results. Especially, HRR/RecSBP and HRR/RecDBP were significantly correlated with induced syncope with a sensitivity and specificity ([60%, 83%] cut-off, 0.31; [72%, 80%] cut-off, 0.63). In the Cox regression, HRR/ RecDBP were significantly associated with recurrence of VVS with hazard ratio of 3.29 (confidence interval, 0.95 to 11.3; p = 0.049). CONCLUSION: HRR/RecDBP may be a useful predictor for induction during HUT and recurrence during follow-up in the VVS.


Assuntos
Teste de Esforço , Síncope Vasovagal/diagnóstico , Teste da Mesa Inclinada , Adolescente , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Síncope Vasovagal/fisiopatologia , Adulto Jovem
14.
BMJ Open ; 8(2): e019048, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29439074

RESUMO

OBJECTIVES: The predictors of pacing-induced cardiomyopathy (PICM) for complete atrioventricular block (CAVB) have not yet been defined. The aim of this study was to investigate the major determinant of the occurrence of PICM. SETTING: This is a multicentre, retrospective analysis of CAVB from tertiary referral centres in Daejeon, South Korea. PARTICIPANTS: A cohort of 900 consecutive patients with an implanted pacemaker was collected from December 2001 to August 2015. Of these, a total of 130 patients with CAVB with pacing-dependent rhythm who underwent ECG and echocardiogram before and after implantation were analysed for the occurrence of PICM. OUTCOME MEASURES: Cox proportional hazards models evaluated the determinant of PICM by ECG, device parameters and echocardiogram over a mean of 4.5 years. RESULTS: PICM was observed in 16.1% (n=21) of all patients with CAVB (age, 64±11 years; male, 36.2%). The preimplant left ventricular (LV) ejection fraction (66%±9% vs 66%±8%) and non-apical pacing (40.4% vs 33.3%) were similar; however, the native QRS duration (124±34 ms vs 149±32 ms) and the paced QRS duration (pQRSd) (139±29 ms vs 167±28 ms) were significantly different between the two groups. The postimplant LV ejection fraction (61%±7% vs 31%±8%) was also significantly different at the end of follow-up. A pQRSd significantly correlated with PICM (HR 1.05, 95% CI 1.02 to 1.09, P=0.001). A pQRSd with a cut-off value of above 140 ms had a sensitivity of 95% while a pQRSd with a cut-off value of above 167 ms had a specificity of 90% for PICM. CONCLUSION: In patients with CAVB with pacing-dependent rhythm, regardless of the pacing site, the pQRSd is a major determinant of the occurrence of PICM.


Assuntos
Bloqueio Atrioventricular/terapia , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/epidemiologia , Ventrículos do Coração/fisiopatologia , Marca-Passo Artificial/efeitos adversos , Idoso , Cardiomiopatias/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Curva ROC , República da Coreia/epidemiologia , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda
15.
Yonsei Med J ; 59(2): 258-264, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29436194

RESUMO

PURPOSE: Comparisons of rhythm and rate control strategies for stroke prevention in patients with atrial fibrillation (AF) are still inconclusive. We compared differences in clinical outcomes between the rhythm and rate control strategies. MATERIALS AND METHODS: The COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry prospectively enrolled 6000 patients who were treated for AF using real-world guideline adherence at multiple referral centers. In total, 2508 (41.8%) patients were clinically followed up for over six months. Of these, 1134 (45.2 %) patients treated by rhythm control and 1374 (54.8 %) patients treated by rate control were analyzed for clinical outcomes, including stroke and cardiovascular outcomes. RESULTS: Among all patients (age, 68±10 years; male, 62.4%), those treated with the rhythm control strategy were significantly younger, had more symptomatic paroxysmal AF, and a shorter AF duration, and were less likely to have diabetes, renal dysfunction, and heart failure, compared to those treated with the rate control strategy (CHA2DS2-VASc score 2.4±1.5 vs. 3.1±1.7, p<0.001). Even though oral anticoagulation was similarly prescribed in both groups, occurrence of stroke was less likely to occur in the rhythm control strategy group (0.0% vs. 0.7%, p=0.015). Multivariate Cox hazard regression showed that only age, especially more than 75 years old, were significantly correlated with the occurrence of stroke, regardless of the strategy used for treatment. CONCLUSION: In this prospective AF cohort, compared with the rate control strategy, the rhythm control strategy was associated with fewer cardiovascular events and strokes in a short-term period.


Assuntos
Fibrilação Atrial/fisiopatologia , Frequência Cardíaca/fisiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Administração Oral , Idoso , Antitrombinas/administração & dosagem , Antitrombinas/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
16.
Clin Ther ; 40(1): 50-63.e3, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29248384

RESUMO

PURPOSE: This 8-week study in Korea aimed to evaluate the efficacy and tolerability of a telmisartan/amlodipine + hydrochlorothiazide (TAH) combination versus telmisartan/amlodipine (TA) combination in patients with essential hypertension that did not respond appropriately to 4-week treatment with TA. METHODS: All patients who met the inclusion criteria received TA (40/5 mg) during a 4-week run-in period (period 1). Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], ≥140 and <200 mm Hg, or ≥130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12.5 mg (test group) or TA only (control group). The test and control drugs were administered in each group for 2 weeks (period 2). Patients who completed period 2 underwent 6-week treatment (period 3) with a TAH and TA dose twice that in period 2. The primary end point was the change in MSSBP at week 8 of treatment. Secondary end points were the change in MSSBP at week 2 and MS diastolic BP, BP control rate, and BP response rate at weeks 2 and 8. Treatment tolerability was assessed based on adverse events (AEs), laboratory evaluations (chemistry, hematology, and urinalysis), 12-lead ECG, and physical examination including vital sign measurements. FINDINGS: We randomized 310 patients to the treatment groups. The mean (SD) ages of the TAH and TA groups were 62.0 (10.8) and 63.4 (10.4) years, respectively. The least squares mean change in MSSBP was significantly greater in the TAH group than in the TA group after 8 weeks (-18.7 vs -12.2 mm Hg; P < 0.001). Similar results were obtained on changes in MSSBP after 2 weeks and changes in sitting diastolic BP, BP control rate, and BP response rate at weeks 2 and 8 compared with the respective baseline values. The prevalences of treatment-emergent AEs (29.0% vs 16.3%; P = 0.008) and adverse drug reactions (20.0% vs 10.5%; P = 0.020) were significantly greater in the TAH group than in the TA group. Most treatment-emergent AEs were mild or moderate; none were severe. The most frequently reported AEs were dizziness and headache. IMPLICATION: TAH triple therapy was more effective than was TA double therapy in reducing BP in these patients in Korea with essential hypertension that did not adequately respond to TA. ClinicalTrials.gov identifier: NCT02738632.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Benzoatos/administração & dosagem , Hipertensão Essencial/tratamento farmacológico , Hidroclorotiazida/administração & dosagem , Adulto , Idoso , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Benzoatos/efeitos adversos , Benzoatos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Tontura/induzido quimicamente , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Cefaleia/induzido quimicamente , Humanos , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Telmisartan , Resultado do Tratamento , Adulto Jovem
17.
Int J Mol Med ; 41(1): 373-380, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115450

RESUMO

Tumor necrosis factor­α­mediated (TNF­α) epithelial­mesenchymal transition (EMT) is associated with distant metastasis in patients with colorectal cancer with poor prognosis. Although traditional herbal medicines have long been used to treat colorectal cancer, the incidence and mortality in patients with colorectal cancer has continued to increase. Danggui­Sayuk­Ga­Osuyu­Saenggang­Tang (DSGOST) has long been used for treatment of chills, while few studies have reported its anticancer effect. This study aimed to demonstrate the inhibitory effect of DSGOST on TNF­α­mediated invasion and migration of colorectal cancer HCT116 cell lines. MTT was used to measure cell viability. Wound healing and Τranswell invasion assay were used to detect migration and invasion of cells, respectively. The intracellular localization of proteins of interest was assessed by immunocytochemistry. Western blotting was performed to determine the expression level of various proteins. A non­toxic dose of DSGOST (50 µg/ml) on HCT116 cells was determined by MTT assay. Furthermore, DSGOST prevented the TNF­α­induced invasive phenotype in HCT116 cells. DSGOST inhibition of the invasive phenotype was also associated with increased expression of EMT markers. Furthermore, DSGOST treatment blocked TNF­α­induced migration and invasion of HCT116 cells. In addition, DSGOST treatment inhibited TNF­α­mediated nuclear translocation of Snail. DSGOST treatment also downregulated TNF­α­induced phosphorylation of AKT and glycogen synthase kinase­3ß. Therefore, the findings of the current study suggest that DSGOST exhibits anti­migration and anti­invasion effects in TNF­α­treated HCT116 human colorectal cells.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/química , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/genética , Células HCT116 , Humanos , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Necrose Tumoral alfa/administração & dosagem
18.
Korean J Intern Med ; 33(2): 323-330, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28226202

RESUMO

BACKGROUND/AIMS: Scrub typhus is known as a self-limited infectious disease. Cardiac complication is uncommon and usually not life-threatening. Until now, few cases of fulminant myocarditis by scrub typhus have been reported. So, we investigated incidence and predictors of acute myocarditis in severe scrub typhus. METHODS: We retrospectively reviewed 89 patients among 91 scrub typhus confirmed patients who examined an echocardiogram and cardiac biomarkers from 2005 to 2015 in the intensive care unit at our hospital. We excluded two patients who didn't have electrocardiography. Patients were divided into two groups and compared between scrub typhus with (n = 13) and without (n = 76) acute myocarditis. RESULTS: Age, sex, and underlying diseases were similar between the groups. The existence of eschar and duration of general ache and fever were similar between the groups. However, patients with acute myocarditis had more elevated total bilirubin, high incidence of ST elevations and paroxysmal atrial fibrillation (PAF) than those without acute myocarditis. Receiver operating characteristic analysis showed that the PAF was a predictor of myocarditis with a sensitivity of 70% and specificity of 84%. Predictive power of combination of ST-segment elevation and PAF was significantly associated with myocarditis in the multivariate analysis (odds ratio, 1.57; 95% confidence interval [CI], 1.21 to 11.7; p = 0.041) and area under the curve was 0.947 (95% CI, 0.878 to 0.983; p < 0.001). CONCLUSIONS: Acute myocarditis with scrub typhus may be more common than previously reported. Patients with high bilirubin and PAF are at increased risk of acute myocarditis with scrub typhus. These patients warrant closer follow-up and echocardiogram would be needed.


Assuntos
Miocardite/etiologia , Tifo por Ácaros/complicações , Doença Aguda , Idoso , Feminino , Febre/etiologia , Humanos , Masculino , Miocardite/diagnóstico , Miocardite/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/epidemiologia
19.
Oncotarget ; 8(51): 88386-88400, 2017 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-29179443

RESUMO

Drug markets revisits herbal medicines, as historical usages address their therapeutic efficacies with less adverse effects. Moreover, herbal medicines save both cost and time in development. SH003, a modified version of traditional herbal medicine extracted from Astragalus membranaceus (Am), Angelica gigas (Ag), and Trichosanthes Kirilowii Maximowicz (Tk) with 1:1:1 ratio (w/w) has been revealed to inhibit tumor growth and metastasis on highly metastatic breast cancer cells, both in vivo and in vitro with no toxicity. Meanwhile, autophagy is imperative for maintenance cellular homeostasis, thereby playing critical roles in cancer progression. Inhibition of autophagy by pharmacological agents induces apoptotic cell death in cancer cells, resulting in cancer treatment. In this study, we demonstrate that SH003-induced autophagy via inhibiting STAT3 and mTOR results in an induction of lysosomal p62/SQSTM1 accumulation-mediated reactive oxygen species (ROS) generation and attenuates tumor growth. SH003 induced autophagosome and autolysosome formation by inhibiting activation of STAT3- and mTOR-mediated signaling pathways. However, SH003 blocked autophagy-mediated p62/SQSTM1 degradation through reducing of lysosomal proteases, Cathepsins, resulting in accumulation of p62/SQSTM1 in the lysosome. The accumulation of p62/SQSTM1 caused the increase of ROS, which resulted in the induction of apoptotic cell death. Therefore, we conclude that SH003 suppresses breast cancer growth by inducing autophagy. In addition, SH003-induced p62/SQSTM1 could function as an important mediator for ROS generation-dependent cell death suggesting that SH003 may be useful for treating breast cancer.

20.
Clin Ther ; 39(10): 2049-2060, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28939406

RESUMO

PURPOSE: The goal of this study was to compare the efficacy and safety of fixed-dose combinations of amlodipine/losartan potassium/chlorthalidone (A/L/C) and A/L in Korean patients with stage 2 hypertension inadequately controlled by A/L. METHODS: This study was an 8-week, randomized double-blind, multicenter, phase III clinical trial. Three hundred forty volunteer patients with stage 2 hypertension were randomized to receive A/L/C or A/L. The primary end point was a change in sitting systolic blood pressure (SitSBP) after 8 weeks of treatment. As secondary end points, the change in SitSBP after 2 weeks of treatment and the change in sitting diastolic blood pressure (SitDBP) were compared between treatment groups. All patients were assessed for adverse events, clinical laboratory data, and vital signs. FINDINGS: Of 330 patients from 33 medical centers, 328 patients who had available efficacy data were analyzed. After 8 weeks of double-blind treatment, the mean (SD) changes in SitSBP at 8 weeks were -16.4 (0.9) mm Hg and -6.9 (1.0) mm Hg in the A/L/C and A/L groups, respectively. A/L/C had a statistically superior blood pressure-lowering effect compared with that of A/L (mean [SD] difference, 9.5 [1.3] mm Hg; P < 0.001). The mean (SD) change in SitDBP at 8 weeks was significantly greater with A/L/C (-8.0 [0.6] mm Hg) than with A/L (-3.6 [0.6] mm Hg) (P < .001). In terms of the mean (SD) change in SitDBP at 2 weeks compared with baseline, A/L/C (-5.9 [0.5] mm Hg) was statistically different from A/L (-2.9 [0.5] mm Hg) (P < .001). Mean (SD) SitSBP change from baseline to week 2 was -13.2 (0.9) and -5.5 (0.9) in the A/L/C and A/L groups, respectively, with a statistically significant blood pressure-lowering effect (P < 0.001). The number of participants who achieved target blood pressure at week 8 was significantly higher in the A/L/C group (93 patients [55.7%]) than in the A/L group (48 [29.8%]) (P < 0.001). Adverse drug reactions were observed in 23 patients (7.0%), and the incidence of dizziness was significantly higher in the A/L/C group than in the A/L group (4.8% vs 0.6%, P = 0.037) There were no serious adverse events associated with the study drugs. IMPLICATIONS: The results of this study suggest that A/L/C had a significantly increased blood pressure-lowering efficacy compared with that of A/L and had a good safety profile. ClinicalTrials.gov identifier: NCT02916602.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Clortalidona/administração & dosagem , Hipertensão/tratamento farmacológico , Losartan/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Clortalidona/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/fisiopatologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...