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1.
Sci Rep ; 14(1): 9705, 2024 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678158

RESUMEN

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.


Asunto(s)
Plaquetas , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inmunología , Masculino , Femenino , Persona de Mediana Edad , Plaquetas/inmunología , Estudios de Casos y Controles , Trombocitopenia/sangre , Trombocitopenia/inmunología , Trombocitopenia/etiología , Anciano , Adulto , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Anemia/sangre , Anemia/inmunología , Factores de Riesgo , Citopenia
2.
Eur J Phys Rehabil Med ; 60(2): 319-330, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38358464

RESUMEN

BACKGROUND: Motor control exercise (MCE) is effective in alleviating non-specific chronic low back pain (NCLBP). Neuro-imaging research is warranted to explore the underlying neural mechanisms of MCE. AIM: We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the central mechanism underpinning the effects of MCE in patients with NCLBP. DESIGN: A randomized, single-blinded, controlled trial. SETTING: The setting was out-patient and community. POPULATION: Fifty-eight patients with NCLBP. METHODS: Patients were randomized into the MCE or manual therapy (MT) group. All the participants completed pain-related clinical assessments and rs-fMRI scans before and after intervention. We performed exploratory whole-brain analyses in regional homogeneity (ReHo) and resting-state functional connectivity (rsFC) with significant post-pre differences in ReHo before and after intervention, and investigated associations between imaging and pain-related clinical assessments. RESULTS: Compared with the MT group, a greater alleviation in pain intensity and disability was observed in the MCE group after intervention, and was sustained at the 6-month follow-up (P<0.001). Only the MCE group showed increased ReHo values in the right pre-central gyrus and decreased ReHo values in the bilateral posterior cerebellum (voxel level P<0.001, cluster-level FWE corrected P<0.05). Decreased rsFC of the right posterior cerebellum-left superior parietal gyrus and left insula were significantly positively associated with pain-related disability (voxel level P<0.001, cluster-level FWE corrected P<0.05). CONCLUSIONS: These findings demonstrated that MCE had superior effects in relieving pain and pain-related disability, which might be associated with its modulation of rsFC between the cerebellum and areas involved in sensory-discriminative processing of noxious and somato-sensory stimuli, affection, and cognition. CLINICAL REHABILITATION IMPACT: This study provided preliminary evidence that MCE might alleviate NCLBP through its modulation of the function of brain areas related to chronic pain and postural control. Those results support MCE's clinical application and help physiotherapists to provide better multidisciplinary interventions with the combination of MCE and other first-line treatments.


Asunto(s)
Dolor Crónico , Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/terapia , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Dolor Crónico/diagnóstico por imagen , Dolor Crónico/terapia , Ejercicio Físico
3.
Pain Physician ; 27(1): E55-E64, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38285031

RESUMEN

BACKGROUND: Motor control exercise (MCE) effectively alleviates nonspecific chronic low back pain (CLBP), but the neural mechanisms underlying this phenomenon are poorly understood. OBJECTIVE: To study MCE's neural mechanisms in patients with CLBP by resting-state functional magnetic resonance imaging (rs-fMRI). STUDY DESIGN: A prospective, single-blind, randomized, controlled trial. SETTING: Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University. METHODS: 58 patients were randomly assigned to either the MCE or the Manual Therapy (MT) group. Before and after treatment, all the patients underwent ultrasound imaging to measure transversus abdominis (TrA) activation, rs-fMRI scans and questionnaire assessments. We analyzed the activation and connectivity of the bilateral precuneus based on the fractional amplitude of low-frequency fluctuation (fALFF) and effective connectivity (EC) analyses. Further, we determined the association between imaging and clinical measures. RESULTS: Pain intensity, pain catastrophizing, and pain-related disability were alleviated significantly in both groups post-treatment. However, the MCE group showed a greater reduction in pain-related disability and a better improvement in activation of the right TrA than the MT group. After MCE, patients showed an increase in regional fALFF values in the key node of the default mode network (bilateral precuneus) and decreased EC from the bilateral precuneus to the key node of the frontoparietal network (the left dorsolateral prefrontal cortex (DLPFC)). The pre-to-post-treatment change in the EC from bilateral precuneus into the left DLPFC was significantly correlated with the pre-to-post-treatment change in visual analog scale scores and activation of the right TrA in the MCE group (r = 0.765, P < 0.001 and r = 0.481 and P = 0.043 respectively). LIMITATIONS: The present study showes the correlation between the alteration of brain functions and CLBP-related symptoms, which does not reveal the causal effect between them. Further, this study does not estimate the long-term efficacy of MCE on brain function, and the sample size was not calculated based on fMRI data. CONCLUSION: These findings demonstrate that MCE may alleviate CLBP symptoms in patients by modifying information transmission from the default mode network to the left frontoparietal network.


Asunto(s)
Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Red en Modo Predeterminado , Estudios Prospectivos , Método Simple Ciego , Plasticidad Neuronal
4.
iScience ; 26(12): 108347, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38125021

RESUMEN

It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists.

5.
Eur Thyroid J ; 12(6)2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37855414

RESUMEN

Background: Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients. Methods: We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were then utilized to explore the association between detection routes and PTC-specific and competing mortality. Results: Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04-0.46; P = 0.01) and 0.47 (95% CI: 0.20-1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively. Conclusions: Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.


Asunto(s)
Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/diagnóstico , Estudios Retrospectivos , Neoplasias de la Tiroides/diagnóstico , Riesgo , Incidencia
6.
Comput Intell Neurosci ; 2022: 2784563, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35502351

RESUMEN

Deep learning is good at extracting the required feature quantity from the massive input information through multiple hidden layers and completing the learning through training to achieve the task of load forecasting. The impulse power load data contain a lot of noise, burrs, and strong randomness. As an improved recurrent neural networks, the output of long short-term memory (LSTM) network is not only related to the current input, but also closely related to the historical information, which can effectively predict the impact power load. An impulse power load forecasting model based on improved recurrent neural networks is proposed. To solve the training difficulties caused by deep networks, database is divided into training data set and test data set. To accelerate running speed and improve accuracy and reliability, parameter setting in deep learning neural network is analyzed. The proposed load forecasting model is verified by simulation and compared with the existing methods. Taking the average relative error as the standard, the effectiveness of the proposed model for the forecasting of impulse power load connected to the bus is verified.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Predicción , Memoria a Largo Plazo , Reproducibilidad de los Resultados
7.
Eur J Phys Rehabil Med ; 57(5): 793-806, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33960180

RESUMEN

INTRODUCTION: Chronic low back pain (CLBP) has been recognized as the leading cause of disability. Up to 90% of patients with CLBP are classified as having non-specific CLBP (NSCLBP). Motor control exercise (MCE) is one of the most popular and widespread treatment options, and has many advantages in alleviating pain and disability. This meta-analysis is aimed to investigate the effectiveness of MCE on NSCLBP, disability, and core muscles reported in randomized controlled trials (RCTs). EVIDENCE ACQUISITION: PubMed, Web of Science, and EMBASE were searched from inception to August 2020. Articles were eligible if they were RCTs that evaluated MCE against sham or other treatments in isolation and measured outcomes including pain intensity and disability or core muscles morphologic characteristics. EVIDENCE SYNTHESIS: Two authors independently extracted the data. Eighteen studies of 894 studies with a total of 1333 individuals with NSCLBP were retained for the meta-analysis. Compared with other conservative treatments, MCE was better in reducing pain and disability posttreatment and was better in reducing pain at the 6-month follow-up period. However, it had comparable effects on pain reduction at 12-month and 24-month follow-up period, and on disability at the 6-month, 12-month and 24-month follow-up period. MCE resulted in comparable effects to other treatments in improving the core muscle thickness posttreatment. CONCLUSIONS: Low to very low quality of evidence supported that MCE resulted in a greater reduction of pain and disability posttreatment, and a greater reduction of pain at the 6-month follow-up than other treatments for NSCBLP. The findings in this review further support that MCE may be more effective than other treatments at short-term follow-ups, and at least has equivalent long-term effects to other forms of treatments in NSCLBP.


Asunto(s)
Dolor Crónico , Dolor de la Región Lumbar , Dolor Crónico/terapia , Ejercicio Físico , Humanos , Dolor de la Región Lumbar/terapia , Músculos , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
Opt Lett ; 46(6): 1385-1388, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33720193

RESUMEN

We proposed a passively stabilized Q-switched Er:Lu2O3 laser at 2845 nm, applying a MXene Nb2CTx nanosheets saturable absorber prepared by the liquid-phase exfoliation method. The surface morphology and nonlinear properties of this nanosheet were systematically characterized. Average output power of 542 mW for the Q-switched laser was obtained under 7.26 W of absorbed pump power. Meanwhile, the Q-switched pulse duration was measured to be 223.7 ns with 142.9 kHz repetition rate corresponding to a peak power of 16.96 W.

9.
BMC Public Health ; 21(1): 342, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33579253

RESUMEN

BACKGROUND: Reproductive tract infections (RTIs) have become major but silent public health problems devastating women's lives in Bangladesh. Accurately and precisely identifying high-risk areas of RTIs through high-resolution risk maps is meaningful for resource-limited settings. METHODS: We obtained data reported with RTI symptoms by women of childbearing age in the years 2007, 2011 and 2014 from Bangladesh Demographic and Health Survey. High-spatial Environmental, socio-economic and demographic layers were downloaded from different open-access data sources. We applied Bayesian spatial-temporal models to identify important influencing factors and to estimate the infection risk at 5 km spatial resolution across survey years in Bangladesh. RESULTS: We estimated that in Bangladesh, there were approximate 11.1% (95% Bayesian credible interval, BCI: 10.5-11.7%), 13.9% (95% BCI: 13.3-14.5%) and 13.4% (95% BCI: 12.8-14.0%) of women of childbearing age reported with RTI symptoms in 2007, 2011 and 2014, respectively. The risk of most areas shows an obvious increase from 2007 to 2011, then became stable between 2011 and 2014. High risk areas were identified in the southern coastal areas, the western Rajshahi Division, the middle of Khulna Division, and the southwestern Chittagong Division in 2014. The prevalence of Rajshahi and Nawabganj District were increasing during all the survey years. CONCLUSION: The high-resolution risk maps of RTIs we produced can guide the control strategies targeted to priority areas cost-effectively. More than one eighth of women of childbearing age reported symptoms suggesting RTIs and the risk of RTIs varies in different geographical area, urging the government to pay more attention to the worrying situation of female RTIs in the country.


Asunto(s)
Infecciones , Infecciones del Sistema Genital , Bangladesh/epidemiología , Teorema de Bayes , Femenino , Humanos , Prevalencia
10.
Pain Res Manag ; 2020: 9629526, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33193926

RESUMEN

Purpose: Pain catastrophizing may contribute to the altered trunk muscle activity in patients with nonspecific chronic low back pain (NSCLBP). It is unclear if pain catastrophizing influences static postural control in patients with NSCLBP. This study aimed to investigate the relationship between pain catastrophizing and static postural control in NSCLBP patients. Methods: Sixty-eight participants with NSCLBP and 40 healthy participants were recruited. Postural control was assessed by the sway area and the sway length of the center of pressure (COP) during balance tests. Pain catastrophizing in participants with NSCLBP was assessed by the Pain Catastrophizing Scale (PCS). Bilateral transversus abdominis (TrA) activation was evaluated by ultrasound imaging-measured percent change in muscle thickness. Associations between COP parameter and PCS/subscales of PCS were examined by multiple linear regression (MLR). Results: Our results observed a larger COP sway area in NSCLBP group under eyes-closed condition (p < 0.001) and a lower level of voluntary activation of the bilateral TrA (p < 0.001), compared with the healthy control group. The MLR analyses revealed that the COP area sway under eyes-closed condition was significantly associated with the PCS score/helplessness score of PCS, voluntary activation of the left TrA, and age in participants with NSCLBP (ß = 0.222/0.236, 0.341/0.344, and 0.328/0.325; p=0.045/0.033, 0.002, and 0.004, resp.). Conclusions: Static postural control was associated with pain catastrophizing, voluntary activation of TrA, and age in participants with NSCLBP. This indicated that pain catastrophizing may affect postural control and should be considered when interpreting balance test results and managing NSCLBP.


Asunto(s)
Músculos Abdominales/diagnóstico por imagen , Músculos Abdominales/fisiología , Catastrofización/diagnóstico por imagen , Dolor Crónico/diagnóstico por imagen , Dolor de la Región Lumbar/diagnóstico por imagen , Equilibrio Postural/fisiología , Adulto , Catastrofización/epidemiología , Dolor Crónico/epidemiología , Estudios Transversales , Femenino , Humanos , Dolor de la Región Lumbar/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven
11.
Appl Opt ; 59(27): 8066-8070, 2020 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-32976383

RESUMEN

Titanium carbide (TiC) nanosheets of two-dimensional multilayer structure were prepared by the liquid-phase exfoliation method. By using the TiC as a saturable absorber, a stable passively Q-switched Er:Lu2O3 laser at 2.85 µm was realized. Under an absorbed pump power of 7.32 W, the obtained maximum output power was 896 mW with a slope efficiency of 15.6%. The Q-switched pulse duration was measured to be 266.8 ns with repetition rates of 136.9 kHz, corresponding to a peak power of 24.6 W.

12.
Artículo en Inglés | MEDLINE | ID: mdl-32210171

RESUMEN

BACKGROUND: Diarrhea in children under five years of age remains a challenge in reducing child mortality in Nepal. Understanding the spatiotemporal patterns and influencing factors of the disease is important for control and intervention. METHODS: Data regarding diarrhea prevalence and its potential influencing factors were extracted from the Demographic and Health Surveys in Nepal and other open-access databases. A Bayesian logistic regression model with district-specific spatio-temporal random effects was applied to explore the space and time patterns of diarrhea risk, as well as the relationships between the risk and the potential influencing factors. RESULTS: Both the observed prevalence and the estimated spatiotemporal effects show a decreasing diarrhea risk trend from 2006 to 2016 in most districts of Nepal, with a few exceptions, such as Achham and Rasuwa. The disease risk decreased with mothers' years of education (OR 0.93, 95% Bayesian Credible Interval (BCI) 0.87, 0.997). Compared to spring, autumn and winter had lower risks of diarrhea. The risk firstly increased and then decreased with age and children under 12-24 months old were the highest risk group (OR 1.20, 95% BCI 1.04, 1.38). Boys had higher risk than girls (OR 1.24, 95% BCI 1.13, 1.39). Even though improved sanitation wasn't found significant within a 95% BCI, there was 93.2% of chance of it being a protective factor. There were no obvious spatiotemporal clusters among districts and each district tended to have its own spatiotemporal diarrhea prevalence pattern. CONCLUSIONS: The important risk factors identified by our Bayesian spatial-temporal modeling provide insights for control and intervention on children diarrhea in Nepal. Special attention should be paid to high risk groups of children and high risk seasons, as well as districts with high risk or increased trend of risk. Effective actions should be implemented to improve sanitation and women's education level. District-specific control planning is recommended for local governments for effective control of children diarrhea in Nepal.


Asunto(s)
Diarrea , Teorema de Bayes , Preescolar , Demografía , Diarrea/epidemiología , Femenino , Encuestas Epidemiológicas , Humanos , Lactante , Masculino , Nepal/epidemiología , Análisis Espacio-Temporal
13.
Artículo en Inglés | MEDLINE | ID: mdl-30987085

RESUMEN

Background: Hand, foot, and mouth disease (HFMD) is a common infectious disease among children. Guangdong Province is one of the most severely affected provinces in south China. This study aims to identify the spatiotemporal distribution characteristics and potential predictors of HFMD in Guangdong Province and provide a theoretical basis for the disease control and prevention. Methods: Case-based HFMD surveillance data from 2009 to 2012 was obtained from the China Center for Disease Control and Prevention (China CDC). The Bayesian spatiotemporal model was used to evaluate the spatiotemporal variations of HFMD and identify the potential association with meteorological and socioeconomic factors. Results: Spatially, areas with higher relative risk (RR) of HFMD tended to be clustered around the Pearl River Delta region (the mid-east of the province). Temporally, we observed that the risk of HFMD peaked from April to July and October to December each year and detected an upward trend between 2009 and 2012. There was positive nonlinear enhancement between spatial and temporal effects, and the distribution of relative risk in space was not fixed, which had an irregular fluctuating trend in each month. The risk of HFMD was significantly associated with monthly average relative humidity (RR: 1.015, 95% CI: 1.006-1.024), monthly average temperature (RR: 1.045, 95% CI: 1.021-1.069), and monthly average rainfall (RR: 1.004, 95% CI: 1.001-1.008), but not significantly associated with average GDP. Conclusions: The risk of HFMD in Guangdong showed significant spatiotemporal heterogeneity. There was spatiotemporal interaction in the relative risk of HFMD. Adding a spatiotemporal interaction term could well explain the change of spatial effect with time, thus increasing the goodness of fit of the model. Meteorological factors, such as monthly average relative humidity, monthly average temperature, and monthly average rainfall, might be the driving factors of HFMD.


Asunto(s)
Enfermedad de Boca, Mano y Pie/epidemiología , Teorema de Bayes , Niño , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Conceptos Meteorológicos , Modelos Estadísticos , Riesgo , Factores Socioeconómicos , Temperatura
14.
Oncol Lett ; 15(4): 5013-5019, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29552137

RESUMEN

Vincristine is one of the most common anticancer drugs clinically employed in the treatment of various malignancies. A major side effect associated with vincristine is the development of neuropathic pain, which is not readily relieved by available analgesics. Although efforts have been made to identify the pathogenesis of vincristine-induced neuropathic pain, the mechanisms underlying its pathogenesis have not been fully elucidated. In the present study, a neuropathic pain model was established in Sprague-Dawley rats by intraperitoneal injection of vincristine sulfate. The results demonstrated that vincristine administration induced the upregulation of transient receptor potential cation channel subfamily V member 1 (TRPV1) protein expression and current density in dorsal root ganglion (DRG) nociceptive neurons. Consistently, inhibition of TRPV1 with capsazepine alleviated vincristine-induced mechanical allodynia and thermal hyperalgesia in rats. Furthermore, vincristine administration induced the upregulation of tumor necrosis factor (TNF)-α production in DRGs, and inhibition of TNF-α synthesis with thalidomide in vivo reversed TRPV1 protein expression, as well as pain hypersensitivity induced by vincristine in rats. The present results suggested that TNF-α could sensitize TRPV1 by promoting its expression, thus leading to mechanical allodynia and thermal hyperalgesia in vincristine-treated rats. Taken together, these findings may enhance our understanding of the pathophysiological mechanisms underlying vincristine-induced pain.

15.
Bioorg Chem ; 77: 16-24, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29316508

RESUMEN

In this study, a series of novel naphthalimide-polyamine conjugates modified by alkylation at the terminal of the polyamine chain were synthesized. These novel conjugates were evaluated for their anti-cancer activities. The results revealed that the length of the polyamine chain and the terminal alkyl group had influences on anticancer activities. Compound 3g was chosen to further study the anti-cancer mechanism and evaluate the anti-tumor efficacy in vivo. It induced intrinsic apoptosis and suppressed migration of hepatoma cells. The preliminary studies of compound 3gin vivo showed that it might be a promising candidate for cancer therapy.


Asunto(s)
Antineoplásicos/farmacología , Naftalimidas/farmacología , Poliaminas/farmacología , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Alquilación , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Naftalimidas/química , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Poliaminas/química , Relación Estructura-Actividad , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/metabolismo , Cicatrización de Heridas/efectos de los fármacos
16.
J Med Chem ; 60(5): 2071-2083, 2017 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-28177238

RESUMEN

Approximately 90% of cancer-associated deaths result from disseminated tumors, indicating the ineffectiveness of current therapies and the imperative need of antimetastatic drugs. A novel pharmacophore with flavonoid and naphthalimide moieties was constructed by using a fragment-based drug design and a series of eight flavone-naphthalimide-polyamine conjugates were synthesized. In vitro evaluation revealed that compound 6c with a homospermidine motif displayed better cell selectivity between cancerous and normal liver cells than amonafide did. The in vivo assays on two hepatocellular carcinoma (HCC) models verified that 6c potently suppressed pulmonary metastasis with improved organ indexes compared to amonafide. Various experiments showed that 6c as a potential fluorescent chemical probe could target the mitochondria. Preliminary investigation into the mechanism of action of 6c indicated that it might harness a polyamine transporter for cell entrance, localize in the mitochondria, selectively cause reactive oxygen species (ROS) overproduction in hepatoma cells instead of normal liver cells, and finally lead to HCC cell apoptosis and migration inhibition via multiple ROS-mediated signaling pathways.


Asunto(s)
Flavonas/farmacología , Mitocondrias/efectos de los fármacos , Naftalimidas/farmacología , Metástasis de la Neoplasia/prevención & control , Poliaminas/farmacología , Línea Celular , Diseño de Fármacos , Humanos , Especies Reactivas de Oxígeno/metabolismo
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