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1.
J Biochem ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34086898

RESUMO

Transmembrane protein 168 (TMEM168) was found to be localized on the nuclear membrane. A heterozygous mutation (c.1616G>A, p. R539Q) in TMEM168 was identified in patients with Brugada syndrome. This mutation reduced expression of cardiomyocyte sodium channel Nav1.5 via Nedd4-2 E3 ubiquitin ligase-induced ubiquitination and degradation. However, the detailed molecular mechanism provoked by the TMEM168 mutant remains unclear. Here, we demonstrated that small heat shock protein αB-crystallin, which can bind to Nav1.5 and Nedd4-2 and interfere with the association of both proteins, was strongly recruited from the cell surface to the perinuclear region because of the much higher interaction of αB-crystallin with the TMEM168 mutant than with wild-type TMEM168. Following knockdown of αB-crystallin in HL-1 cardiomyocytes, the interaction of Nav1.5 with Nedd4-2 was increased, despite a reduction of the expression level of Nav1.5. Moreover, αB-crystallin-mediated reduction of Nav1.5 expression was rescued in the presence of a proteasome inhibitor MG-132, suggesting the importance of the αB-crystallin-modulated ubiquitin-proteasome system for the stability of Nav1.5 expression. Collectively, the balance of molecular interactions among Nav1.5, Nedd4-2, and αB-crystallin plays a role in the regulation of cardiomyocyte cell surface expression of Nav1.5, and the TMEM168 mutant disturbs this balance, resulting in a decrease in Nav1.5 expression.

2.
J Cardiol ; 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34130873

RESUMO

BACKGROUND: Brain or B-type natriuretic peptide (BNP) is an objective marker to diagnose the presence of heart failure (HF) and assess its severity. However, the determinants of serum BNP level in elderly patients with severe aortic valve stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) have not been well investigated. METHODS: We prospectively studied 106 AS patients who underwent TAVI. Cardiac catheterization, transesophageal echocardiography, and blood collection for plasma BNP level measurements were performed simultaneously just before the TAVI procedures. RESULTS: Ninety-nine patients (83.9±5.0 years, 33% male) were studied. The natural logarithm of BNP (lnBNP) level was 5.4±0.9 pg/mL. Significant correlations with lnBNP level were observed in: 1) the history of syncope, prior HF medication, and New York Heart Association class III or IV (R=0.255, p=0.011) (R=0.210, p=0.037) (R=0.402, p<0.001), 2) albumin and hemoglobin level (R=-0.289, p=0.004) (R=0.263, p=0.009), 3) Left ventricular (LV) ejection fraction and global longitudinal strain (LVGLS) (R=-0.338, p<0.001) (R=0.447, p<0.001), 4) LV end-diastolic volume index (EDVI), LV mass index, and left atrial volume index (R=0.280, p=0.005) (R=0.366, p<0.001) (R=0.337, p<0.001), 5) the catheter-measured pressure gradient across the aortic valve (AVPG) (R=0.365, p<0.001). Note that LV wall stress was not significantly correlated with lnBNP level. LVGLS, AVPG, hemoglobin level, and LVEDVI were independently correlated with ln BNP level (R=0.652, LVGLS; ß=0.395, p<0.006, AVPG; ß=0.291, p=0.001, hemoglobin level; ß=-0.216, p=0.011, and LVEDVI; ß=0.203, p=0.016, respectively). CONCLUSIONS: In severe AS patients candidate for TAVI, multiple factors, including the severities of AS and HF conditions and subclinical LV dysfunction determined by LVGLS affects plasma BNP level.

3.
J Biol Chem ; : 100761, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33971198

RESUMO

Diabetes mellitus (DM) causes injury to tissues and organs, including to the heart and kidney, resulting in increased morbidity and mortality. Thus, novel potential therapeutics are continuously required to minimize DM-related organ damage. We have previously shown that dipeptidyl peptidase III (DPPIII) has beneficial roles in a hypertensive mouse model, but it is unknown whether DPPIII has any effects on DM. In this study, we found that intravenous administration of recombinant DPPIII in diabetic db/db mice for eight weeks suppressed the DM-induced cardiac diastolic dysfunctions and renal injury without alteration of the blood glucose level. This treatment inhibited inflammatory cell infiltration and fibrosis in the heart, and blocked the increase in albuminuria by attenuating the disruption of the glomerular microvasculature and inhibiting the effacement of podocyte foot processes in the kidney. The beneficial role of DPPIII was, at least in part, mediated by the cleavage of a cytotoxic peptide, named Peptide 2, which was increased in db/db mice compared with normal mice. This peptide consisted of nine amino acids, was a digested fragment of complement component 3 (C3), and had an anaphylatoxin-like effect determined by the Miles assay and chemoattractant analysis. The effect was dependent on its interaction with the C3a receptor and protein kinase C-mediated RhoA activation downstream of the receptor in endothelial cells. In conclusion, DPPIII plays a protective role in the heart and kidney in a DM animal model through cleavage of a peptide that is a part of C3.

4.
Protein J ; 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34008140

RESUMO

Macrophage proliferation is known to correlate with macrophage accumulation in atherosclerotic plaque, and therefore its inhibition and secondary reduction of plaque inflammation may have therapeutic beneficial effects on atherosclerosis. Recently, we reported that a peptide corresponding to positions 41-51 of royalisin (which consists of 51 amino acid residues), a potent antibacterial protein contained in royal jelly (RJ), can specifically bind to oxidized LDL (Ox-LDL), a major components of atherosclerotic lesions. Here, we investigated the interaction of RJ proteins including royalisin with LDL and Ox-LDL. Measurement of LDL oxidation by the production of thiobarbituric acid reactive substances and conjugated dienes, and by electrophoretic mobility on polyacrylamide gel electrophoresis showed that RJ proteins including royalisin and the degradation products of major RJ protein (MRJP) 1 and MRJP3 can induce oxidation of LDL and Ox-LDL. Surface plasmon resonance experiments showed that these RJ proteins can exhibit much higher binding affinity to LDL than Ox-LDL (the equilibrium dissociation constant, KD = 8.35 and 49.65 µg proteins/mL for LDL and Ox-LDL, respectively). Experiments using cultured mouse J774A.1 macrophage cells proved that these RJ proteins can inhibit macrophage proliferation markedly and concentration-dependently, regardless of the absence or presence of LDL and Ox-LDL, but hardly affect lipid accumulation in macrophages. These results suggest that RJ proteins including royalisin and degradation products of MRJP1/MRJP3 may have therapeutic beneficial effects on atherosclerosis owing to the reduction of plaque inflammation. Further studies of these RJ proteins may lead to the discovery of novel anti-atherosclerotic drugs.

7.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805673

RESUMO

5-Fluorouracil (5-FU) is a cornerstone drug used in the treatment of colorectal cancer (CRC). However, the development of resistance to 5-FU and its analogs remain an unsolved problem in CRC treatment. In this study, we investigated the molecular mechanisms and tumor biological aspects of 5-FU resistance in CRC HCT116 cells. We established an acquired 5-FU-resistant cell line, HCT116RF10. HCT116RF10 cells were cross-resistant to the 5-FU analog, fluorodeoxyuridine. In contrast, HCT116RF10 cells were collaterally sensitive to SN-38 and CDDP compared with the parental HCT16 cells. Whole-exome sequencing revealed that a cluster of genes associated with the 5-FU metabolic pathway were not significantly mutated in HCT116 or HCT116RF10 cells. Interestingly, HCT116RF10 cells were regulated by the function of thymidylate synthase (TS), a 5-FU active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) inhibiting enzyme. Half of the TS was in an active form, whereas the other half was in an inactive form. This finding indicates that 5-FU-resistant cells exhibited increased TS expression, and the TS enzyme is used to trap FdUMP, resulting in resistance to 5-FU and its analogs.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , Timidilato Sintase/genética , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Floxuridina/farmacologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Irinotecano/farmacologia , Compostos de Platina/farmacologia , Timidilato Sintase/metabolismo , Sequenciamento Completo do Exoma
8.
BMJ Open ; 11(4): e046681, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33853804

RESUMO

OBJECTIVES: Functional status assessments of activities of daily living may improve prognostic precision during initial diagnostic evaluations in young and middle-aged adults with cancer. However, the association between pretreatment functional status and survival in these patients is poorly understood. This study aimed to evaluate the prognostic value of functional status in young and middle-aged patients with cancer. DESIGN: Multicentre retrospective cohort study. SETTING: We used a cancer registry from Osaka Prefecture, Japan. The data were linked to administrative claims data from 35 hospitals in the same prefecture. PARTICIPANTS: Patients aged 18-69 years who received new diagnoses of gastric, colorectal or lung cancer between 2010 and 2014. MAIN OUTCOME MEASURE: Cox proportional hazards models of 5-year all-cause mortality were developed to examine the prognostic impact of pretreatment functional status, which was categorised into three levels of functional disability (none, moderate and severe) based on Barthel Index scores. The models controlled for age, sex, comorbidities, cancer stage and tumour histology. RESULTS: We analysed 12 134 patients. Higher mortality risks were significantly associated with moderate functional disability (adjusted HR 1.44 (95% CI 1.18 to 1.75), 1.35 (95% CI 1.08 to 1.68) and 1.74 (95% CI 1.50 to 2.03) in patients with gastric, colorectal and lung cancer, respectively) and severe functional disability (adjusted HR 3.56 (95% CI 2.81 to 4.51), 2.37 (95% CI 1.89 to 2.95) and 2.34 (95% CI 2.00 to 2.75) in patients with gastric, colorectal and lung cancer, respectively). CONCLUSION: Accounting for functional status at cancer diagnosis may improve the prediction of survival time in young and middle-aged adults with cancer. Functional status has potential applications in survival predictions and risk adjustments when analysing outcomes in patients with cancer.


Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Atividades Cotidianas , Adolescente , Adulto , Idoso , Neoplasias Colorretais/diagnóstico , Estado Funcional , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Adulto Jovem
9.
J Nat Med ; 75(3): 532-539, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33712999

RESUMO

OGATA Koan (1810-63) was a physician and the director of Tekijuku, and he contributed to Western medicine in the late Edo period. Osaka University preserves two of his medicine chests. One of the chests, which was used in his last years (the second chest) contained 22 glass bottles and 6 wooden cylinders. These bottles and cylinders contained formulated medicines; however, about half cannot be opened because of the long-term storage. It is necessary to comprehend the physical property of both the containers and their contents for investigation of this adequate preservation method; however, destructive analysis is not allowed. To analyze the medicines sealed in the glass bottles, we focused on muonic X-ray analysis, which has high transmittance. First, we certified the analytical methods using a historical medicinal specimen preserved in Osaka University. Thereafter, we applied the method on the bottles stored in the second chest. X-ray fluorescence identified the glass of those bottles to be lead potash glass. Among these bottles, we chose the bottle with the label "," which contains white powdered medication, for muonic X-ray analysis. We identified the contents of the medication in the glass to be Hg2Cl2. Through this study, we first applied muonic X-ray analysis on the medical inheritances and succeeded to detect the elements contained both in the container and in the contents of the sealed bottle. This would be a new method for nondestructive analysis of such cultural properties.


Assuntos
Produtos Biológicos/análise , Produtos Biológicos/história , História do Século XIX , Humanos , Japão , Farmacognosia , Raios X
10.
Int J Cardiol ; 333: 98-104, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33647363

RESUMO

BACKGROUND: We evaluated the 1-year success rate of maintaining sinus rhythm after catheter ablation (CA) for atrial fibrillation (AF) in patients with or without congestive heart failure (CHF). METHODS: In this single-centre retrospective matched-pair cohort study of 3,018 AF patients who underwent initial CA between January 2012 and June 2018, 227 pairs with (CHF group) or without CHF (control group) were matched using propensity scores. In the CHF group, 108 patients were assigned to the arrhythmia-induced cardiomyopathy (AIC) group whose left ventricular systolic dysfunction was explained only by lasting AF or atrial tachycardia; the remaining 119 had organic heart diseases (non-AIC group). We evaluated the 1-year AF-free survival and changes in clinical findings before and after CA. RESULTS: The CHF and control groups showed similar AF-free survival; however, AIC patients had significantly better survival than non-AIC patients. AF recurrence was significantly related to CHF re-hospitalisation, which was significantly more frequent in the non-AIC group than in the AIC group. The clinical outcomes of left atrial dilation, brain natriuretic peptide level, and left ventricular ejection function improved significantly before and after CA in both groups. The degree of improvement was significantly better in the AIC group than in the non-AIC group. CONCLUSIONS: The 1-year success rate was not significantly different between the CHF and control groups. The 1-year success rate in the AIC group was similar to that in the AIC-control group and was better than that in the non-AIC group. CHF clinical outcomes were improved significantly.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Estudos de Coortes , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
11.
BMC Cancer ; 21(1): 264, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691661

RESUMO

BACKGROUND: Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan. METHODS: Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test. RESULTS: Among 275,720 newly diagnosed cancer patients, 21,784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer. CONCLUSIONS: The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options.


Assuntos
Segunda Neoplasia Primária/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros/estatística & dados numéricos , Neoplasias Gástricas/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias Uterinas/epidemiologia , Adulto Jovem
12.
J Cardiovasc Electrophysiol ; 32(5): 1251-1258, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33713521

RESUMO

INTRODUCTION: Non-pulmonary vein (PV) triggers are a major cause of atrial tachyarrhythmia (ATA) recurrence after catheter ablation. However, the effect of the diagnosis-to-ablation time (DAT) on non-PV triggers in persistent atrial fibrillation is unknown. METHODS AND RESULTS: This observational study evaluated 502 consecutive persistent AF patients who underwent initial ablation. We compared 408 patients whose DAT was <3 years with 94 patients whose DAT was ≥3 years. Following PV and posterior wall isolation, 193 non-PV triggers, including 50 AFs, 30 atrial tachycardias (ATs), and 113 repetitive atrial premature beats, were elicited and ablated in 137 (27%) patients. Specifically, 80 non-PV AF/AT triggers were provoked in 64 (13%) patients, being identified more frequently in the DAT ≥ 3 years group than in the DAT < 3 years group (20% vs. 11%, p = .025) especially with a higher prevalence of coronary sinus/inferior left atrial triggers. During a median follow-up of 770 days, the ATA recurrence-free rate was higher in the DAT < 3 years group than the DAT ≥ 3 years group (79% vs. 53% at 2 years, p < .001). In a multivariate analysis, female sex (odds ratio: 2.70, p = .002) and a longer DAT (odds ratio: 1.13/year, p = .008) were predictors of non-PV AF/AT triggers, and a longer DAT (hazard ratio: 1.12/year, p < .001) and non-PV AT/AF triggers (hazard ratio: 1.79, p = .009) were associated with ATA recurrence. CONCLUSION: Early ablation after the first diagnosis of persistent AF may reduce emerging non-PV AF/AT triggers and ATA recurrence.

13.
Cancer Res ; 81(9): 2318-2331, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33757977

RESUMO

The growth and progression of cancers are crucially regulated by the tumor microenvironment where tumor cells and stromal cells are mutually associated. In this study, we found that stomatin expression was markedly upregulated by the interaction between prostate cancer cells and stromal cells. Stomatin suppressed cancer cell proliferation and enhanced apoptosis in vitro and inhibited xenograft tumor growth in vivo. Stomatin inhibited Akt activation, which is mediated by phosphoinositide-dependent protein kinase 1 (PDPK1). PDPK1 protein stability was maintained by its binding to HSP90. Stomatin interacted with PDPK1 and interfered with the PDPK1-HSP90 complex formation, resulting in decreased PDPK1 expression. Knockdown of stomatin in cancer cells elevated Akt activation and promoted cell increase by promoting the interaction between PDPK1 and HSP90. Clinically, stomatin expression levels were significantly decreased in human prostate cancer samples with high Gleason scores, and lower expression of stomatin was associated with higher recurrence of prostate cancer after the operation. Collectively, these findings demonstrate the tumor-suppressive effect of stromal-induced stomatin on cancer cells. SIGNIFICANCE: These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis.

14.
Int Heart J ; 62(2): 390-395, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731531

RESUMO

Perivascular adipose tissue (PVAT) secretes large amounts of inflammatory mediators and plays a certain role in atherosclerosis formation from the exterior of the vessel. In the present study, we examined the expression level of inflammation-related mediators using adipose tissue samples harvested from patients with and without coronary artery disease (CAD). The subjects were 23 patients who underwent elective coronary bypass surgery (CAD group) and 17 patients who underwent elective mitral valve surgery (non-CAD group) between January 2017 and March 2018. The adipose tissue was harvested from three sites: the ascending aorta (AO), subcutaneous fat (SC), and pericoronary artery (CO) for the measurement of the expression levels of interleukin (IL) -1ß, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (INF) -γ, and arginase (Arg) -1. In both the non-CAD and CAD groups, the expression levels of all mediators, except Agr-1, which showed a tendency to have higher levels in the SC than in the AO and CO, tended to upregulate in the AO than in the SC and CO. The CAD group had higher values of almost all mediators, except Arg-1. Most importantly, the expression levels of IL-1ß, IL-6, and IL-10 in the coronary artery were significantly higher in the CAD group. The expression levels of inflammatory mediators in the pericoronary adipose tissue were significantly higher in the CAD than in the non-CAD group. The adipose tissue appears to influence atherosclerosis formation from the exterior of the coronary artery.


Assuntos
Tecido Adiposo/metabolismo , Aterosclerose/metabolismo , Doença da Artéria Coronariana/metabolismo , Mediadores da Inflamação/metabolismo , Idoso , Aterosclerose/diagnóstico , Biomarcadores/metabolismo , Vasos Coronários , Feminino , Humanos , Masculino
15.
Front Immunol ; 12: 620541, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763067

RESUMO

Tenascin-C (TNC) is an extracellular matrix glycoprotein that is expressed during embryogenesis. It is not expressed in normal adults, but is up-regulated under pathological conditions. Although TNC knockout mice do not show a distinct phenotype, analyses of disease models using TNC knockout mice combined with in vitro experiments revealed the diverse functions of TNC. Since high TNC levels often predict a poor prognosis in various clinical settings, we developed a transgenic mouse that overexpresses TNC through Cre recombinase-mediated activation. Genomic walking showed that the transgene was integrated into and truncated the Atp8a2 gene. While homozygous transgenic mice showed a severe neurological phenotype, heterozygous mice were viable, fertile, and did not exhibit any distinct abnormalities. Breeding hemizygous mice with Nkx2.5 promoter-Cre or α-myosin heavy chain promoter Cre mice induced the heart-specific overexpression of TNC in embryos and adults. TNC-overexpressing mouse hearts did not have distinct histological or functional abnormalities. However, the expression of proinflammatory cytokines/chemokines was significantly up-regulated and mortality rates during the acute stage after myocardial infarction were significantly higher than those of the controls. Our novel transgenic mouse may be applied to investigations on the role of TNC overexpression in vivo in various tissue/organ pathologies using different Cre donors.

16.
Protein J ; 40(2): 192-204, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33665770

RESUMO

Cytosolic estrogen sulfotransferase (SULT1E) mainly catalyzes the sulfate conjugation of estrogens, which decrease atherosclerosis progression. Recently we reported that a YKEG sequence in human SULT1E1 (hSULT1E1) corresponding to residues 61-64 can bind specifically to oxidized low-density lipoprotein (Ox-LDL), which plays a major role in the pathogenesis of atherosclerosis; its major oxidative lipid component lysophosphatidylcholine (LPC), and its structurally similar lipid, platelet-activating factor (PAF). In this study, we investigated the effect of Ox-LDL on the sulfating activity of hSULT1E1. In vivo experiments using a mouse model of atherosclerosis showed that the protein expression of SULT1E1 was higher in the aorta of mice with atherosclerosis compared with that in control animals. Results from a sulfating activity assay of hSULT1E1 using 1-hydroxypyrene as the substrate demonstrated that Ox-LDL, LPC, and PAF markedly decreased the sulfating activity of hSULT1E1, whereas native LDL and 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) as one of the oxidized phosphatidylcholines showed the opposite effect. The sulfating activity greatly changed in the presence of LPC, PAF, and POVPC in their concentration-dependen manner (especially above their critical micelle concentrations). Moreover, Ox-LDL specifically recognized dimeric hSULT1E1. These results suggest that the effects of Ox-LDL and native LDL on the sulfating activity of hSULT1E1 might be helpful in elucidating the novel mechanism underlying the pathogenesis of atherosclerosis, involving the relationship between estrogen metabolism, LDL, and Ox-LDL.

17.
Cancer Sci ; 112(3): 1150-1160, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33428808

RESUMO

This study focused on children as well as adolescents and young adults (AYAs) and aimed to examine trends in survival of leukemia over time using population-based cancer registry data from Osaka, Japan. The study subjects comprised 2254 children (0-14 years) and 2,905 AYAs (15-39 years) who were diagnosed with leukemia during 1975-2011. Leukemia was divided into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and other leukemias. We analyzed 5-year overall survival probability (5y-OS), using the Kaplan-Meier method and expressed time trends using the joinpoint regression model. For recently diagnosed (2006-2011) patients, a Cox proportional hazards model was applied to determine predictors of 5y-OS, using age group, gender, and treatment hospital as covariates. Over the 37-year period, 5y-OS greatly improved among both children and AYAs, for each leukemia type. Among AYAs, 5y-OS of ALL improved, especially after 2000 (65% in 2006-2011), when the pediatric regimen was introduced but was still lower than that among children (87% in 2006-2011, P < .001). Survival improvement was most remarkable in CML, and its 5y-OS was over 90% among both children and AYAs after the introduction of molecularly targeted therapy with tyrosine kinase inhibitors. Among patients with recently diagnosed AML, the risk of death was significantly higher for patients treated at nondesignated hospitals than those treated at designated cancer care hospitals. The changes in survival improvement coincided with the introduction of treatment regimens or molecularly targeted therapies. Patient centralization might be one option which would improve survival.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mieloide Aguda/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Adolescente , Adulto , Fatores Etários , Institutos de Câncer/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-33159266

RESUMO

PURPOSE: We examined the characteristics of non-pulmonary vein (PV) triggers in repeat ablation after cryoballoon ablation for paroxysmal atrial fibrillation (PAF). METHODS: This study evaluated 119 patients undergoing a second ablation procedure for recurrent atrial tachyarrhythmia (ATA) after cryoballoon PV isolation (CB-PVI) for PAF. RESULTS: Fifty-three of 119 (45%) patients had PV reconnection. All reconnected PVs were isolated. No non-PV triggers were elicited in 42/119 (35%) patients (NNPV group). In 77/119 (65%) patients, 139 isoproterenol-induced non-PV triggers, including 45 triggers that initiated AF, were identified. Non-PV triggers initiating AF were observed at the superior vena cava (SVC), left atrial posterior wall (LAPW) including the PV antra, interatrial septum, right atrium, left atrial appendage/mitral anulus, and coronary sinus in 14 (12%), 10 (8%), 8 (7%), 7 (6%), 4 (3%), and 2 (2%) patients, respectively. Non-PV triggers originated from only the SVC and/or LAPW including the PV antra, and the SVC and/or LAPW was isolated in 18/119 (15%) patients (SVC/LAPW group). Non-PV triggers originating from other sites were focally ablated in 59/119 (50%) patients (OS group). During a median 461 days of follow-up, 39/42 (93%), 17/18 (94%), and 38/59 (64%) patients in the NNPV, SVC/LAPW, and OS groups, respectively, remained ATA recurrence-free. The recurrence rate was higher in the OS group than in the NNPV (P = 0.005) or SVC/LAPW groups (P = 0.042). CONCLUSIONS: Over half of patients had non-PV triggers at subsequent ablation after CB-PVI. Non-PV triggers from the SVC/LAPW can be eliminated more successfully than triggers from other sites.

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