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Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed.
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Mieloma Múltiple , Supervivencia sin Progresión , Humanos , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Ensayos Clínicos como Asunto , Neoplasia Residual , BiomarcadoresRESUMEN
INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRv, also referred to as hATTR; ORPHA 271861) and wild-type ATTR amyloidosis (ATTRwt; ORPHA 330001) are rare, progressive, systemic protein misfolding disorders with heterogeneous clinical presentations. ATTRv and ATTRwt amyloidosis are characterized by the deposition of amyloid fibrils in multiple organs including the heart, nerves, eyes, and soft tissues. The management of ATTR amyloidosis is complex because of its multisystemic nature and progression despite available treatment options. Morbidity is high and there are many unmet medical needs for patients. While contemporary ATTR amyloidosis cohorts are diagnosed earlier, have lower risk disease and lower mortality compared with the previous era, these advances coupled with the emergence of effective disease-modifying therapies have confounded the design of future prospective clinical trials and interpretation of historical control data. MAIN BODY: The Amyloidosis Forum is a public-private partnership between the US Food and Drug Administration Center for Drug Evaluation and Research and the nonprofit Amyloidosis Research Consortium ( www.arci.org ). This article summarizes proceedings from the 21 June 2023 Amyloidosis Forum on advancing drug development in ATTR amyloidosis in an evolving treatment landscape. The Forum focused on elements of clinical trial design to address these challenges and discussed their strengths and weaknesses from multiple stakeholder perspectives (i.e., patient, sponsor, statistician, clinician, and regulatory authorities). CONCLUSION: Given rapid evolution of natural history in ATTR amyloidosis, the utility of historical control data is limited. Leveraging contemporary real-world data is essential for clinical trial design. Evidence generation from clinical trials should address clinically relevant questions. Key factors in successful trial design must be informed by up-to-date data on natural history, prognostic factors, clinically meaningful thresholds, and sharing available clinical trial data. The Amyloidosis Forum includes the community of patients with ATTR amyloidosis, the physicians who treat them, and the sponsors and regulators who collectively stand ready to support further studies in order to develop novel effective therapies.
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Neuropatías Amiloides Familiares , Desarrollo de Medicamentos , Humanos , Neuropatías Amiloides Familiares/tratamiento farmacológico , Benzoxazoles/uso terapéutico , OligonucleótidosRESUMEN
Talent construction is the cornerstone to the establishment of a high-quality, homogeneous healthcare system in a healthcare consortium. Pulmonary and critical care medicine (PCCM) as the first pilot specialty, the standardized training of PCCM specialists has started and achieved remarkable results. The consortium member hospitals' physician specialist education is an important complement to PCCM training. The establishment of the consortium provides a new form of the education of physicians in PCCM, with the advantages of high quality teaching, wide coverage of staff and throughout the career development process. This article summarized the current status of physician specialty education in the member hospitals of the consortium, and further proposes the goal of homogenized specialty education for physicians in the member hospitals. And it analyzed in depth the problems that existed in the practice of training for hospital consortium member hospitals specialists, such as non-uniform level of instruction, non-systematic content of training, limited sources of teaching cases, and lack of teaching materials and equipment. For the medical consortium member hospital physician specialty education of in-depth thinking, we put forward the corresponding countermeasures. The aim of this study is to explore the homogenization of the specialty education system of pulmonary and critical care medicine in the member hospitals, in order to comprehensively improve the medical level of respiratory specialists in the member hospitals of the medical consortium.
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Cuidados Críticos , Neumología , Neumología/educación , Humanos , Hospitales , EspecializaciónRESUMEN
The article "MicroRNA-375 accelerates the invasion and migration of colorectal cancer through targeting RECK", by L.-J. Wei, D.-M. Bai, Z.-Y. Wang, B.-C. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4738-4745-DOI: 10.26355/eurrev_201906_18055-PMID: 31210300 has been retracted by the authors for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/0E5B55962B277F3D0ABBC0451DAAB3). In particular, concerns were raised about Figure 3 and Table I. Unfortunately, the authors are not able to confirm nor deny this concern as they did not find the primary data for figures. The authors decided to study this experiment again to deliver more precise results. After consultation among the authors, in line with the rigorous attitude towards scientific research, authors agreed that it was necessary to withdraw the article and make further research and improvement. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18055.
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OBJECTIVE: To study the potential mechanism of Lactobacillus crispatus inhibiting cervical squamous intraepithelial lesion (SIL) and screen the early warning factors of SIL. METHODS: The effects of Lactobacillus crispatus on the proliferation, apoptosis, cross pore migration and invasion and cytokines of cervical precancerous cells Ect1/E6E7 were detected respectively. The effect of Lactobacillus crispatus on the expression of differential proteins screened in Ect1/E6E7 cells were detected by Western blot. RESULTS: Lactobacillus crispatus significantly inhibited the proliferation, induced apoptosis and inhibited cell migration of Ect1/E6E7 cells in a time-dependent manner (P < 0.05), but had no significant effect on cell invasion. Lactobacillus crispatus significantly promoted the secretion of Th1 cytokines and inhibited the secretion of Th2 cytokines by Ect1/E6E7 cells (P < 0.05). In addition, compared with SiHa cells in the control group, the expression of differential proteins PCNA, ATM, LIG1 and HMGB1 in Ect1/E6E7cells decreased significantly, while the expression of TDG and OGG1 proteins increased significantly (P < 0.05). ABCG2 protein in Ect1/E6E7 cells was slightly higher than that in SiHa cells, but the difference was not statistically significant. What is interesting is that Lactobacillus crispatus significantly inhibited the expression of ABCG2, PCNA, ATM, LIG1, OGG1 and HMGB1 proteins in Ect1/E6E7 cells, and promoted the expression of TDG protein. CONCLUSIONS: Lactobacillus crispatus may inhibit the function of Ect1/E6E7 cells through multiple pathways and exert the potential to reverse the progression of SIL.
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OBJECTIVE: To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. METHODS: A "admission-hospitalization-discharge" whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. RESULTS: The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = -7.688, -3.576 and -4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). CONCLUSIONS: The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients' cure.
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Ascitis , Esquistosomiasis , Humanos , Pacientes Internos , Educación en Salud , Hospitalización , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Objective: To construct a novel prognostic nomogram model based on more comprehensive variables for patients with small-cell lung cancer (SCLC). Methods: The data of 722 patients with SCLC confirmed by pathology in Affiliated Cancer Hospital of Shanxi Medical University from January 2015 to December 2018 were retrospectively analyzed [including 592 males and 130 females, aged from 23 to 82(61±9) years]. A random seed count of 133 was used to divide those patients into training set (n=422) and validation set (n=300). Kaplan-Meier was used for survival curves analysis and univariate Log-rank test was used for evaluating the influence of clinical variables on the prognosis of sclc, variables with P<0.05 in univariate analysis were included in a multivariate Cox regression model. The nomogram was constructed based on the variables which P<0.05 in multivariate analysis. Receiver operating characteristic (ROC) curve, calibration by Integrated Brier score (IBS) and clinical net benefit by decision curve analysis (DCA) were used to evaluate model discriminative power, prediction error value, and clinical net benefit, and compared with the American Joint Committee on Cancer 8th TNM. Results: Male, abnormal monocyte (MON) counts, abnormal neuron specific enolase (NSE), abnormal cytokeratin 19 fragment (Cyfra211), M1a stage, M1b stage, M1c stage, radiotherapy (RT), chemotherapy ≥4 cycles and prophylactic cranial irradiation (PCI) were prognostic factors for SCLC[HR(95%CI)=1.39(1.00-1.92), 1.29(1.02-1.63), 1.41(1.11-1.80), 2.02(1.48-2.76), 1.09(0.77-1.55), 1.44(0.94-2.22), 2.01(1.49-2.71), 0.75(0.57-0.98), 0.40(0.31-0.51)and 0.42(0.26-0.68), respectively, all P<0.05]. The area under ROC curve (AUC) of the nomogram in training set and validation set were 0.814(95%CI: 0.765-0.862)and 0.787 (95%CI: 0.725-0.849), which were higher than TNM [0.616(95%CI: 0.558-0.674) and 0.648(95%CI: 0.581-0.715)].The calibration curve showed a good correlation between the nomogram prediction and actual observation for the 2-year overall survival (OS). IBS indicted a lower prediction error rate (training set: 0.132 vs 0.169; validation set: 0.138 vs 0.169). DCA showed a wider threshold range than TNM (training set: 0.01-0.96 vs 0.01-0.85, validation set: 0.01-0.94 vs 0.01-0.86) and a greater improvement of the clinical net benefit (in training set the nomogram had a greater clinical benefit than TNM in the range of 0.19-0.96, and remained in validation set in the range of 0.19-0.94). Conclusion: The established nomogram model for predicting 2-year OS in patients with SCLC based on 8 variables, including gender, MON, NSE, Cyfra211, M stage, RT, CT cycles and PCI can be used for an more accurately prognosis prediction and reference for therapeutic regimen selection.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Nomogramas , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The t-year mean survival or restricted mean survival time (RMST) has been used as an appealing summary of the survival distribution within a time window [0, t]. RMST is the patient's life expectancy until time t and can be estimated nonparametrically by the area under the Kaplan-Meier curve up to t. In a comparative study, the difference or ratio of two RMSTs has been utilized to quantify the between-group-difference as a clinically interpretable alternative summary to the hazard ratio. The choice of the time window [0, t] may be prespecified at the design stage of the study based on clinical considerations. On the other hand, after the survival data have been collected, the choice of time point t could be data-dependent. The standard inferential procedures for the corresponding RMST, which is also data-dependent, ignore this subtle yet important issue. In this paper, we clarify how to make inference about a random "parameter." Moreover, we demonstrate that under a rather mild condition on the censoring distribution, one can make inference about the RMST up to t, where t is less than or even equal to the largest follow-up time (either observed or censored) in the study. This finding reduces the subjectivity of the choice of t empirically. The proposal is illustrated with the survival data from a primary biliary cirrhosis study, and its finite sample properties are investigated via an extensive simulation study.
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Esperanza de Vida , Simulación por Computador , Humanos , Modelos de Riesgos Proporcionales , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate the role of long non-coding RNA (lncRNA) CACNA1G-AS1 in regulating proliferative and invasive abilities of colorectal cancer (CRC) cells by mediating p53, thus influencing the progression of CRC. PATIENTS AND METHODS: CACNA1G-AS1 level in CRC tissues and adjacent normal tissues was first determined. Its level in CRC patients with different tumor stages was detected as well. Changes in proliferative and invasive abilities of HCT116 and SW480 cells influenced by CACNA1G-AS1 were evaluated. Subcellular distribution of CACNA1G-AS1 was analyzed. Through Western blot, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assay, the interaction between CACNA1G-AS1 and EZH2 was assessed. The biological function of the target gene of CACNA1G-AS1 was finally explored. RESULTS: CACNA1G-AS1 was upregulated in CRC tissues compared to adjacent normal ones. Its level remained higher in CRC patients with stage III-IV compared to those with stage I-II. Knockdown of CACNA1G-AS1 reduced proliferative and invasive abilities of HTC116 and SW480 cells. CACNA1G-AS1 was mainly distributed in the nucleus. Moreover, CACNA1G-AS1 was verified to interact with EZH2. Knockdown of CACNA1G-AS1 or EZH2 upregulated p53 level and decreased the recruitment ability of EZH2 on p53. Finally, p53 knockdown could partially reverse the regulatory effect of CACNA1G-AS1 on the proliferative ability of HCT116 cells. CONCLUSIONS: CACNA1G-AS1 downregulates p53 level by forming a carcinogenic complex with EZH2, thereby enhancing the proliferative and invasive abilities of CRC cells.
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Canales de Calcio Tipo T/metabolismo , Neoplasias Colorrectales/metabolismo , Regulación hacia Abajo , ARN Largo no Codificante/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Canales de Calcio Tipo T/genética , Proliferación Celular , Células Cultivadas , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , ARN Largo no Codificante/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
OBJECTIVE: This study aims to detect the expression pattern of microRNA-375 in colorectal cancer (CRC), and to examine its specific mechanism in regulating the progression of CRC. PATIENTS AND METHODS: We detected microRNA-375 expression in 50 pairs of CRC and paracancerous tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between microRNA-375 expression and pathological indexes of CRC patients was analyzed. Cellular expression of microRNA-375 in CRC cell lines was detected as well. Regulatory effect of microRNA-375 on biological behaviors of CRC cells was examined, including proliferative, invasive and migratory abilities. We used bioinformatics method to predict the potential target of microRNA-375 and finally explored their interactive functions in regulating CRC progression. RESULTS: MicroRNA-375 expression remained higher in CRC tissues relative to paracancerous ones. CRC patients with a high level of microRNA-375 tended to have higher rates of lymph node metastasis and distant metastasis compared with those with a low level. Transfection of microRNA-375 inhibitor greatly reduced proliferative, invasive and migratory abilities of CRC cells. RECK was predicted to be the target of microRNA-375, which was downregulated in CRC tissues and cells. Besides, RECK expression was negatively regulated by microRNA-375 in CRC. Rescue experiments confirmed that microRNA-375/RECK axis promoted the malignant progression of CRC. CONCLUSIONS: MicroRNA-375 is upregulated in CRC, and correlated to lymph node metastasis and distant metastasis. MicroRNA-375 enhances invasive and migratory abilities of CRC cells via regulating RECK.
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Neoplasias Colorrectales/metabolismo , Proteínas Ligadas a GPI/metabolismo , MicroARNs/metabolismo , Anciano , Movimiento Celular , Proliferación Celular , Células Cultivadas , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Proteínas Ligadas a GPI/genética , Perfilación de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Transducción de Señal/genéticaRESUMEN
Objective: To investigate the dose-response relationship between hemoglobin concentration and preterm birth, during pregnancy. Methods: With Zhuang ethnicity, a total of 12 780 pregnant women and their infants that admitted to WumingãPingguoãJingxiãDebaoãLongan and Tiandong hospitals, were recruited, in Guangxi Zhuang Autonomous Region, from January 2015 to December 2017. Non-conditional logistic regression method was used to analyze the effect of anemia on preterm birth during pregnancy. Dose-response relationship between hemoglobin concentration and preterm birth was explored, using the restrictive cubic spline model. Results: After excluding 2 053 pregnant women with hypertension or aged 35 years and over, results from the non-conditional logistic regression analysis showed that the risk of preterm birth in the anemia group was 1.29 times (OR=1.29, 95%CI: 1.04-1.59, P=0.019) of the non-anemia group in the first trimester. Data from the restricted cubic sample showed that there appeared nonlinear "L" dose-response relationship between hemoglobin concentration and preterm birth in the first trimester and "U" shape in the third trimester (non-linearity test P<0.001). Conclusion: There appeared nonlinear dose-response relationship between the hemoglobin concentration and preterm birth, both in the first and third trimesters.
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Anemia/complicaciones , Retardo del Crecimiento Fetal/epidemiología , Hemoglobinas/metabolismo , Trabajo de Parto Prematuro/epidemiología , Nacimiento Prematuro/epidemiología , Adulto , China/epidemiología , Femenino , Retardo del Crecimiento Fetal/etiología , Humanos , Recién Nacido , Trabajo de Parto Prematuro/etiología , Embarazo , Complicaciones Hematológicas del Embarazo , Resultado del Embarazo , Mujeres Embarazadas , Factores de RiesgoRESUMEN
For a two-group comparative study, a stratified inference procedure is routinely used to estimate an overall group contrast to increase the precision of the simple two-sample estimator. Unfortunately, most commonly used methods including the Cochran-Mantel-Haenszel statistic for a binary outcome and the stratified Cox procedure for the event time endpoint do not serve this purpose well. In fact, these procedures may be worse than their two-sample counterparts even when the observed treatment allocations are imbalanced across strata. Various procedures beyond the conventional stratified methods have been proposed to increase the precision of estimation when the naive estimator is consistent. In this paper, we are interested in the case when the treatment allocation proportions vary markedly across strata. We study the stochastic properties of the two-sample naive estimator conditional on the ancillary statistics, the observed treatment allocation proportions and/or the stratum sizes, and present a biased-adjusted estimator. This adjusted estimator is asymptotically equivalent to the augmentation estimators proposed under the unconditional setting. Moreover, this consistent estimation procedure is also equivalent to a rather simple procedure, which estimates the mean response of each treatment group first via a stratum-size weighted average and then constructs the group contrast estimate. This simple procedure is flexible and readily applicable to any target patient population by choosing appropriate stratum weights. All the proposals are illustrated with the data from a cardiovascular clinical trial, whose treatment allocations are imbalanced.
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Interpretación Estadística de Datos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sesgo , Humanos , Modelos Estadísticos , Modelos de Riesgos Proporcionales , Distribución Aleatoria , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
In comparing two treatments via a randomized clinical trial, the analysis of covariance (ANCOVA) technique is often utilized to estimate an overall treatment effect. The ANCOVA is generally perceived as a more efficient procedure than its simple two sample estimation counterpart. Unfortunately, when the ANCOVA model is nonlinear, the resulting estimator is generally not consistent. Recently, various nonparametric alternatives to the ANCOVA, such as the augmentation methods, have been proposed to estimate the treatment effect by adjusting the covariates. However, the properties of these alternatives have not been studied in the presence of treatment allocation imbalance. In this article, we take a different approach to explore how to improve the precision of the naive two-sample estimate even when the observed distributions of baseline covariates between two groups are dissimilar. Specifically, we derive a bias-adjusted estimation procedure constructed from a conditional inference principle via relevant ancillary statistics from the observed covariates. This estimator is shown to be asymptotically equivalent to an augmentation estimator under the unconditional setting. We utilize the data from a clinical trial for evaluating a combination treatment of cardiovascular diseases to illustrate our findings.
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BACKGROUND: Most phase-3 trials feature time-to-first event end points for their primary and secondary analyses. In chronic diseases, where a clinical event can occur >1 time, recurrent-event methods have been proposed to more fully capture disease burden and have been assumed to improve statistical precision and power compared with conventional time-to-first methods. METHODS: To better characterize factors that influence statistical properties of recurrent-event and time-to-first methods in the evaluation of randomized therapy, we repeatedly simulated trials with 1:1 randomization of 4000 patients to active versus control therapy, with true patient-level risk reduction of 20% (ie, relative risk=0.80). For patients who discontinued active therapy after a first event, we assumed their risk reverted subsequently to their original placebo-level risk. Through simulation, we varied the degree of between-patient heterogeneity of risk and the extent of treatment discontinuation. Findings were compared with those from actual randomized clinical trials. RESULTS: As the degree of between-patient heterogeneity of risk increased, both time-to-first and recurrent-event methods lost statistical power to detect a true risk reduction and confidence intervals widened. The recurrent-event analyses continued to estimate the true relative risk (0.80) as heterogeneity increased, whereas the Cox model produced attenuated estimates. The power of recurrent-event methods declined as the rate of study drug discontinuation postevent increased. Recurrent-event methods provided greater power than time-to-first methods in scenarios where drug discontinuation was ≤30% after a first event, lesser power with drug discontinuation rates of ≥60%, and comparable power otherwise. We confirmed in several actual trials of chronic heart failure that treatment effect estimates were attenuated when estimated via the Cox model and that increased statistical power from recurrent-event methods was most pronounced in trials with lower treatment discontinuation rates. CONCLUSIONS: We find that the statistical power of both recurrent-events and time-to-first methods are reduced by increasing heterogeneity of patient risk, a parameter not included in conventional power and sample size formulas. Data from real clinical trials are consistent with simulation studies, confirming that the greatest statistical gains from use of recurrent-events methods occur in the presence of high patient heterogeneity and low rates of study drug discontinuation.
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Ensayos Clínicos Fase III como Asunto/métodos , Determinación de Punto Final , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Fármacos Cardiovasculares/uso terapéutico , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Simulación por Computador , Interpretación Estadística de Datos , Determinación de Punto Final/estadística & datos numéricos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Hospitalización , Humanos , Modelos Estadísticos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Recurrencia , Proyectos de Investigación/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.
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Carcinoma Hepatocelular/prevención & control , Proteína Quinasa Activada por ADN/metabolismo , Dieta/efectos adversos , Fructosa-Bifosfato Aldolasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/prevención & control , Proteínas Nucleares/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor , Restricción Calórica , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Movimiento Celular , Proliferación Celular , Proteína Quinasa Activada por ADN/genética , Femenino , Fructosa-Bifosfato Aldolasa/genética , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Proteínas Nucleares/genética , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We demonstrate that a bipolar non-volatile resistive switching behaviour with negative differential resistance (NDR) effect is realized in a Cu/BaTiO3/Ag device, which was deposited on a Si substrate via magnetron sputtering equipment. We suggest that the bipolar resistive switching is dominated by the trapping/detrapping of electrons at the BaTiO3-Cu interface. In addition, we demonstrate that the device exhibits good performance, including a large on/off ratio, high reliability and long retention time. Therefore, BaTiO3 may become a good candidate for application in resistive switching random access memory (RRAM) devices.
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A 3.5 nm amorphous CoFeB film was sputtered on GaAs (001) wafer substrate without applying magnetic field during deposition, and a significant in-plane uniaxial magnetic anisotropy (UMA) field (Hu) of about 300 Oe could be achieved. To precisely determine the intrinsic Gilbert damping constant (α) of this film, both ferromagnetic resonance (FMR) and time-resolved magneto-optical Kerr effect (TRMOKE) techniques were utilized. With good fitting of the dynamic spectra of FMR and TRMOKE, α is calculated to be 0.010 and 0.013, respectively. Obviously, the latter is 30% larger than the former, which is due to the transient heating effect during the TRMOKE measurement. In comparison with ordinary amorphous CoFeB films with negligible magnetic anisotropies, α is enhanced significantly in the CoFeB/GaAs(001) film, which may be mainly resulted from the enhanced spin-orbit coupling induced by the CoFeB/GaAs interface. However, the significant in-plane UMA plays minor role in the enhancement of α.