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1.
Am J Hum Genet ; 111(9): 1953-1969, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39116879

RESUMEN

While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis. Here, we demonstrate the selfish nature of the SMAD4 DNMs causing Myhre syndrome (MYHRS). By analyzing 16 informative trios, we show that MYHRS-causing DNMs originated on the paternally derived allele in all cases. We document a statistically significant epidemiological paternal age effect of 6.3 years excess for fathers of MYHRS probands. We developed an ultra-sensitive assay to quantify spontaneous MYHRS-causing SMAD4 variants in sperm and show that pathogenic variants at codon 500 are found at elevated level in sperm of most men and exhibit a strong positive correlation with donor's age, indicative of a high apparent germline mutation rate. Finally, we performed in vitro assays to validate the peculiar functional behavior of the clonally selected DNMs and explored the basis of the pathophysiology of the different SMAD4 sperm-enriched variants. Taken together, these data provide compelling evidence that SMAD4, a gene operating outside the canonical RAS-MAPK signaling pathway, is associated with selfish spermatogonial selection and raises the possibility that other genes/pathways are under positive selection in the aging human testis.


Asunto(s)
Mutación de Línea Germinal , Discapacidad Intelectual , Proteína Smad4 , Humanos , Masculino , Proteína Smad4/genética , Discapacidad Intelectual/genética , Contractura/genética , Adulto , Facies , Espermatozoides/metabolismo , Espermatozoides/patología , Criptorquidismo/genética , Trastornos del Crecimiento/genética , Deformidades Congénitas de la Mano/genética , Selección Genética , Alelos , Edad Paterna , Testículo/patología , Testículo/metabolismo
2.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(1): 34-39, 2023 Jan 12.
Artículo en Zh | MEDLINE | ID: mdl-36617926

RESUMEN

Objective: To investigate the efficacy and safety of transbronchial cryobiopsy (TBCB) after lung transplantation. Methods: The clinical characteristics, TBCB procedure, diagnosis and treatment, and outcomes of lung transplant recipients of 6 patients (all male, aged 33-67 years) with TBCB in China-Japan Friendship Hospital from May to November 2021 were retrospectively analyzed. Results: Among the 6 patients diagnosed by TBCB, there were 2 cases of organizing pneumonia, 1 acute cellular rejection, 1 antibody-mediated rejection, and 1 bronchiolitis obliterans, and 1 diffuse alveolar damage. After the clinical diagnosis was confirmed, the condition improved after adjustment of the treatments followed. There were no serious complications related to the TBCB procedure. Conclusion: TBCB is valuable and relatively safe in the diagnosis of complications after lung transplantation, but the indications need to be strictly controlled.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Trasplante de Pulmón , Humanos , Masculino , Biopsia/métodos , Broncoscopía/efectos adversos , Broncoscopía/métodos , Pulmón/patología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Anciano
3.
J Med Genet ; 56(7): 427-433, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30803986

RESUMEN

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored. METHODS: Exome sequence data from 1197 AIS cases and 1664 in-house controls was analysed using coverage data to identify rare CNVs. CNV calls were filtered to include only highly confident CNVs with >10 average reads per region and mean log-ratio of coverage consistent with single-copy duplication or deletion. The frequency of 55 common recurrent CNVs was determined and correlated with clinical characteristics. RESULTS: Distal chromosome 16p11.2 microduplications containing the gene SH2B1 were found in 0.7% of AIS cases (8/1197). We replicated this finding in two additional AIS cohorts (8/1097 and 2/433), resulting in 0.7% (18/2727) of all AIS cases harbouring a chromosome 16p11.2 microduplication, compared with 0.06% of local controls (1/1664) and 0.04% of published controls (8/19584) (p=2.28×10-11, OR=16.15). Furthermore, examination of electronic health records of 92 455 patients from the Geisinger health system showed scoliosis in 30% (20/66) patients with chromosome 16p11.2 microduplications containing SH2B1 compared with 7.6% (10/132) of controls (p=5.6×10-4, OR=3.9). CONCLUSIONS: Recurrent distal chromosome 16p11.2 duplications explain nearly 1% of AIS. Distal chromosome 16p11.2 duplications may contribute to scoliosis pathogenesis by directly impairing growth or by altering expression of nearby genes, such as TBX6. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Duplicación Cromosómica , Cromosomas Humanos Par 16 , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Escoliosis/diagnóstico , Escoliosis/genética , Estudios de Casos y Controles , Mapeo Cromosómico , Biología Computacional/métodos , Variaciones en el Número de Copia de ADN , Femenino , Estudios de Asociación Genética/métodos , Heterocigoto , Humanos , Masculino , Fenotipo , Escoliosis/epidemiología , Eliminación de Secuencia , Secuenciación del Exoma
4.
J Interprof Care ; : 1-9, 2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32053408

RESUMEN

Identity development within the interprofessional field is an emerging area of research. This scoping review aims to establish how professional and interprofessional identities are defined, conceptualized, theorized and measured within the interprofessional literature. Six databases were systematically searched for papers focusing on professional and/or interprofessional identities in interprofessional healthcare and education using a scoping review methodology. A total of 84 papers were included. Most papers discussed professional identity only; the minority discussed both identities. There were three key findings. First, no universal definition of interprofessional identity exists. Second, there is no shared understanding of interprofessional identity and its relationship with professional identity. Third, poor alignment between definitions, conceptualizations, theories and measures of interprofessional identity exists. The absence of a psychometrically robust instrument that specifically measures interprofessional identity and the short-term focus of current interprofessional identity research further limits understanding. Research that critically examines professional and interprofessional identity development should be underpinned by clear definitions, concepts, theories and measures of both identities. High-quality research will allow greater understanding of interprofessional identity development and its impact on interprofessional practice.

5.
Haematologica ; 104(12): 2410-2417, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31004019

RESUMEN

Nearly all adults harbor acute myeloid leukemia (AML)-related clonal hematopoietic mutations at a variant allele fraction (VAF) of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow up to investigate associations of clonal mutations of ≥0.0001 allele frequency with future risk of AML. We identified 35 cases with AML that had pre-diagnosis peripheral blood samples and matched two controls without history of cancer per case by sex, age, and ethnicity. We conducted blinded error-corrected sequencing on all study samples and assessed variant-associated risk using conditional logistic regression. We detected AML-associated mutations in 97% of all participants (598 mutations, 5.8/person). Individuals with mutations ≥0.01 variant allele fraction had a significantly increased AML risk (OR 5.4, 95%CI: 1.8-16.6), as did individuals with higher-frequency clones and those with DNMT3A R882H/C mutations. The risk of lower-frequency clones was less clear. In the 11 case-control sets with samples banked ten years apart, clonal mutations rarely expanded over time. Our findings are consistent with published evidence that detection of clonal mutations ≥0.01 VAF identifies individuals at increased risk for AML. Further study of larger populations, mutations co-occurring within the same pre-leukemic clone and other risk factors (lifestyle, epigenetics, etc.), are still needed to fully elucidate the risk conferred by low-frequency clonal hematopoiesis in asymptomatic adults.


Asunto(s)
Biomarcadores de Tumor/genética , Evolución Clonal , Células Clonales/patología , Hematopoyesis , Leucemia Mieloide Aguda/patología , Mutación , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mieloide Aguda/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo
7.
Zhonghua Jie He He Hu Xi Za Zhi ; 40(11): 845-849, 2017 Nov 12.
Artículo en Zh | MEDLINE | ID: mdl-29320832

RESUMEN

Objective: To explore the diagnostic value of endobronchial ultrasonography with a guide sheath (EBUS-GS) for peripheral pulmonary ground glass opacity (GGO). Methods: The clinical data of 27 consecutive patients with 27 GGOs diagnosed by EBUS-GS between November 2014 to December 2015 in our Cancer Hospital were retrospectively analyzed. The average age of these 27 patients, including 9 males and 18 females, was 59±11 years. The median lesion size of the 27 GGOs was 2.9±1.2 cm, including 24 mixed GGOs and 3 pure GGOs. EBUS images of all 27 GGOs were evaluated, cytological, histological and combination diagnosis analyzed, and complications observed. Results: Under thin bronchoscope, 2 out of 27 cases showed bronchial stenosis, 1 showed bronchial stenosis with mucosal swelling, and the other 24 did not show abnormalities. Twenty-five out of 27 GGOs were found by EBUS, including 22 cases of mGGO and 3 of pGGO. In these ultrasonic images of 22 mGGOs, 18 showed mixed blizzard sign, 3 showed diffusely heterogeneous acoustic shadow and 1showed blizzard sign. Ultrasonic images of 3 pGGOs all appeared as blizzard sign. Twenty-six cytological specimens were obtained, and 16 were diagnosed clearly. All 27 histological specimens were collected, and 18 were diagnosed clearly. Nineteen of 27 cases were diagnosed by combination of cytological and histological specimens. One complication of EBUS-GS with mild bleeding was observed, and hemorrhage was terminated by conservative treatment. Conclusions: EBUS-GS is valuable for GGO diagnosis with less complications and higher safety. GGO ultrasonic image manifested as mixed blizzard sign, blizzard sign or diffusely heterogeneous acoustic shadow.


Asunto(s)
Broncoscopía , Neoplasias Pulmonares , Pulmón/diagnóstico por imagen , Ultrasonografía/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
9.
Rev Sci Instrum ; 95(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38758767

RESUMEN

As the plasma beta (ß) increases in high-performance tokamaks, electromagnetic turbulence becomes more significant, potentially constraining their operational range. To investigate this turbulence, a cross-polarization scattering (CPS) diagnostic system is being developed on the HL-3 tokamak for simultaneous measurements of density and magnetic fluctuations. In this work, a quasi-optical system has been designed and analyzed for the Q-band CPS diagnostic. The system includes a lens group for beam waist size optimization, a rotatable wire-grid polarizer for polarization adjustment, and a reflector group for measurement range regulation and system response enhancement. Laboratory tests demonstrated a beam radius of order 4 cm at the target measurement location (near the plasma pedestal), cross-polarization isolation exceeding 30 dB, and poloidal and toroidal angle adjustment ranges of ±40° and ±15°, respectively. These results verify the system's feasibility through laboratory evaluations. The quasi-optical system has been installed on the HL-3 tokamak during the 2023 experimental campaign to support the development of CPS diagnostics.

10.
Rev Sci Instrum ; 94(9)2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37668510

RESUMEN

A 105 GHz collective Thomson scattering (CTS) diagnostic has been successfully developed for fast-ion measurements on the HL-2A tokamak, and it has been deployed during an experimental campaign. Enhanced signals exhibiting synchronous modulation characteristics have been observed across all CTS channels upon the launch of a modulated probe wave. Results show that the intensity of the CTS signal increases with Neutral Beam Injection (NBI) power and is proportional to neutron count, indicating that the scattering signal contains a contribution from fast ions. Compared with the signal without NBI, the enhanced scattering spectrum due to NBI is slightly wider than the predicted fast ion range. Such broadening might be attributed to the heating effects of the gyrotron.

11.
Rev Sci Instrum ; 94(6)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37862534

RESUMEN

Plasma Position Reflectometry (PPR) is planned to provide plasma position and shape information for plasma operation in future fusion reactors. Its primary function is to calibrate the drift of the magnetic signals due to the integral nature of magnetic measurement. Here, we attempt to measure plasma position using ordinary mode (O-mode) and extraordinary mode (X-mode) reflectometry systems on two tokamaks. A new physical model based on the phase shift is proposed to deduce the relative movement of the cut-off layer without density inversion. We demonstrate the plasma position measurements by absolute measurement from density profile inversion and relative measurement from phase shift. The combination of X-mode and O-mode reflectometers can minimize the limitations of single polarization reflectometry and further increase the accuracy of plasma position measurement. These results could provide an important technical basis for the further development of a real-time control system based on PPR.

12.
Eur Rev Med Pharmacol Sci ; 16(15): 2088-91, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23280024

RESUMEN

Asthma is a major epidemic affecting up to one third people in developed countries over the last decades, and making a crucial impact on morbidity rates. The classical characters of asthma in human are airway inflammation, airway hyperreactivity, and airway remodeling. Hygiene hypothesis, inflammation cells and signaling pathway in asthma were involved in Toll-like receptors (TLRs). TLRs are a kind of pattern recognition receptors, which are important in recognition of various pathogens. TLRs have been seen as a key target for asthma treatment, so a promising approach for asthma treatment was adopted to the multiwayly modulating toll-like receptors way.  


Asunto(s)
Asma/tratamiento farmacológico , Receptores Toll-Like/fisiología , Asma/etiología , Asma/inmunología , Humanos , Mastocitos/fisiología , Transducción de Señal
13.
Eur Rev Med Pharmacol Sci ; 26(6): 1868-1875, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35363335

RESUMEN

OBJECTIVE: Clubfoot is a growing public health concern in Bangladesh, with the incidence of approximately 0.64 to 6.8 in every 1000 live births. For over a decade, Ponseti method has been considered a gold standard for treating the clubfoot. Despite few studies have been estimating the number of casts required to correct the clubfoot deformities by Ponseti method, the subject of interest has always remained. Therefore, this current study aimed to investigate the significant predictive factors for the number of casts required to correct congenital clubfoot. PATIENTS AND METHODS: In this retrospective cohort study, we used Bayesian Poisson Regression Model to investigate the influencing factors that could predict how many casts are needed to correct the clubfoot. We included 69 patients with 99 affected feet, who completed their corrective phase of treatment in the Ponseti method. For this cohort study, we integrated only pre-tenotomy casting data with no age restrictions. We used Bayesian Poisson regression analysis technique to estimate the predictive factors. RESULTS: In Bayesian Poisson model, age was the most influencing predictive factor (24.3%) for increasing the number of castings to correct the clubfoot deformity. The clubfoot offspring of the ≤1-year-old was positive, and the incidence rate increased significantly with the casting number. The number of Ponseti casts in male clubfoot children was 28% higher than in female, and this was marginally statistically significant. There was no marked change estimated in the pattern of clubfoot, foot involvement and Pirani score of the severity. CONCLUSIONS: We concluded that the age factor may influence the number of casts required for the correction of clubfoot and specifically ≤ 1-year-old children are highly impacted. Treating clubfoot at an early age is suggested in this study to increase the success of clubfoot treatment and decrease the risk of relapse.


Asunto(s)
Pie Equinovaro , Teorema de Bayes , Moldes Quirúrgicos , Niño , Pie Equinovaro/terapia , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
14.
Rev Sci Instrum ; 93(8): 083518, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050087

RESUMEN

A synthetic electron cyclotron emission (ECE) diagnostic is used to interpret ECE signals from preset plasma equilibrium profiles, including magnetic field, electron density, and electron temperature. According to the simulation results, the electron temperature (Te) profile covering the harmonic overlap region can be obtained by receiving ECE signals at the high field side (HFS) of the HL-2M plasma. The third harmonic ECE at the low field side (LFS) cannot pass through the second harmonic resonance layer at the HFS unless the optical thickness (τ) of the second harmonic becomes gray (τ ≤ 2). In addition, the impact of the relativistic frequency down-shift has been evaluated and corrected. The measurable range of the HFS ECE has been calculated by scanning different parameters (electron density, temperature, and magnetic field). Higher plasma parameters allow a wider radial range of electron temperature measurements. The minimum inner measurable position can reach R = 120 cm (r/a = -0.89) when the product of core temperature (Te0) and density (ne0) is greater than 35 × 1019 keV m-3, which is extended by more than 30 cm inward compared with that of the LFS measurement. The HFS ECE will greatly improve the diagnostic ability of ECE systems on the HL-2M tokamak.

15.
Eur Rev Med Pharmacol Sci ; 25(9): 3614-3622, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34002837

RESUMEN

OBJECTIVE: COVID-19 has become a global public health emergency affecting 223 countries and territories, and it drastically changed the life of public and health care delivery systems. Although many guidelines have been proposed to avoid infection from COVID-19 and to promote the use of telerehabilitation, there is still no clear answer for the current scenario and strategies of therapists' practice during the COVID-19 pandemic lockdown. This study aimed to explore the impact of COVID-19 lockdown on Occupational Therapists' (OTs) practice, the use of telerehabilitation strategies by OTs, and their employment and mental health. Also, this study aimed to explore the OTs perspective on the role of telerehabilitation during this pandemic lockdown. MATERIALS AND METHODS: Online cross-sectional survey was conducted between April 2020 and May 2020. RESULTS: 114 OTs completed the survey. The results of this study showed that 52.8% of therapists had stress and anxiety due to COVID-19 lockdown. We found that 60.7% of OTs (n=65) used telerehabilitation, versus 36.1% (n=39) before the lockdown. Telerehabilitation approaches were mostly implemented during this lockdown for children with autistic problems (66.6%), stroke (12.9%), cerebral palsy (6.4%), learning disabilities (9.6%), Parkinson's diseases (1.6%), and other medical conditions (2.8%). 10% of therapists reported that they lost their job, and 76% reported that this lockdown affected their income negatively. Overall, 87.8% of therapists reported that mobile technology was very useful to overcome the stress due to COVID-19 related lockdown, social isolation, and social distancing. CONCLUSIONS: The COVID-19 pandemic lockdown experiences made us rethink the current approach of therapy services into alternative method (mixed mode) delivery of occupational therapy practice, which is including the combined method of video-based (telerehabilitation) consultation and face to face intervention.


Asunto(s)
COVID-19/epidemiología , Terapia Ocupacional/tendencias , Aceptación de la Atención de Salud , Cuarentena/tendencias , Telerrehabilitación/tendencias , Adulto , Anciano , COVID-19/prevención & control , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/tendencias , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Ocupacional/métodos , Pandemias , Cuarentena/métodos , Telerrehabilitación/métodos , Adulto Joven
16.
Rev Sci Instrum ; 92(8): 083509, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34470419

RESUMEN

A solid state terahertz interferometer has been developed on the recent commissioned HL-2M tokamak. It can work in a wide frequency region of 220-325 GHz, and the terahertz wave is generated from a low frequency phase locked voltage controlled oscillator with the frequency multiplying technique. A phase processor based on field programmable gate array (FPGA) technology is designed for the heterodyne interferometer, and it contributes to real-time display of electron density. To extract phase information, a novel numerical algorithm related to fast Fourier transform is written on the FPGA chip and enables one to obtain phase shift without being affected by amplitude variation induced by plasma absorption or frequency modulation from the outer electromagnetic environment. The interferometer achieves minimum measurable electron density in the order of 1016 m-3. With the plasma diagnosis, electron density and low frequency tearing mode have been measured during the first experimental campaign.

17.
Rev Sci Instrum ; 92(6): 063513, 2021 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-34243534

RESUMEN

Remote control of the diagnostic systems is the basic requirement for the high performance plasma operation in a fusion device. This work presents the development of the remote control system for the multichannel Doppler backward scattering (DBS) reflectometers. It includes a remote controlled quasi-optical system and a remote intermediate frequency (IF) amplifier gain control system. The quasi-optical system contains a rotational polarizer, its polarization angle is tunable through a remote controlled motor, and it could combine the microwave beams with a wide frequency range into one focused beam. The remote IF gain control system utilizes the digital microcontroller (MCU) technique to regulate the signal amplitude for each signal channel. The gain parameters of amplifiers are adjustable, and the feedback of working status in the IF system will be sent to MCU in real time for safe operation. The gain parameters could be controlled either by the Ethernet remote way or directly through the local control interface on the system. Preliminary experimental results show the effectiveness of the remote controlled multichannel DBS system.

18.
Br J Sports Med ; 44(2): 144-7, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18603582

RESUMEN

OBJECTIVE: In this study, the presence and severity of external auditory canal exostoses (EACE) in a group of white water kayakers related to the duration and intensity of kayaking and the number of ear infections reported were identified. DESIGN: A community-based volunteer cross-sectional study was completed with 92 kayakers (69 men, 23 women; mean (SD) age 29.3 (8.72) years) and 65 control volunteers (37 men, 28 women; mean (SD) age 36.9 (14.9) years). After exclusions, 269 individual ears were examined (154 kayakers and 115 controls). Participants completed a questionnaire and underwent otoscopic examination. Main outcome measures were the presence and severity of EACE, the duration and frequency of kayaking and self-reported ear infections. Exclusion criteria included other cold-water exposure, known ear pathology or poor visualisation of the auditory canal. RESULTS: The findings demonstrated that 69.5% of kayaker ears and 1.7% of the control group were found to have EACE. Severity of EACE was significantly associated with the duration (p<0.01) and frequency (p<0.05) of kayaking with 90.6% of kayakers that had participated for more than 10 years having evidence of EACE. A significant relationship also existed between the number of self-reported ear infections and the severity of EACE (p<0.01). CONCLUSION: There is a positive relationship between the duration and frequency of white water kayaking and the presence and severity of EACE and associated ear infections.


Asunto(s)
Conducto Auditivo Externo/patología , Enfermedades del Oído/patología , Exostosis/patología , Deportes , Adulto , Estudios Transversales , Enfermedades del Oído/etiología , Femenino , Humanos , Masculino , Índice de Severidad de la Enfermedad
19.
Eur Rev Med Pharmacol Sci ; 24(10): 5267-5280, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32495860

RESUMEN

OBJECTIVE: To explore possible mechanism of ERBB2 gene expression silencing mediating mitogen-activated protein kinase 1/mitogen-activated protein kinase 3 (MAPK1/MAPK3) signaling pathway on proliferation, migration, and invasion of ovarian cancer cells. PATIENTS AND METHODS: A total of 240 cancer specimens were collected in patients with epithelial ovarian cancer intraoperatively in our hospital from January 2015 to January 2018. Expressions of ERBB2, MAPK1, and MAPK3 in tissues were detected by immunohistochemistry. Following the culture of ovarian cancer cell lines, target cell line with high expression of ERBB2 was screened by qRT-PCR. Cell grouping was performed with four groups after transfection, including Blank group, negative control (NC) group, ERBB2 shRNA group, and ERBB2 overexpression group (shorted as ERBB2 group). The expression levels of ERBB2, MAPK1, MAPK3, vascular endothelial growth factor (VEGF), metalloproteases-2 (MMP-2), and tissue inhibitor of metalloproteases-2 (TIMP-2) were detected by qRT-PCR in different transfection groups, followed by the detection of protein expressions with Western blot. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test the proliferation activity of each group after transfection, while transwell assay and scratch test explored cell invasion and migration in each group, respectively. RESULTS: Immunohistochemistry showed that the positive rates of ERBB2, MAPK1, and MAPK3 in ovarian cancer tissues were significantly increased than those in adjacent normal epithelial tissues. In the cell experiment, ERBB2 gene was highly expressed in SKOV3 ovarian cancer cell line. There was no significant difference in each index between Blank group and NC group (p > 0.05). Compared with Blank group and NC group, the expression levels of ERBB2, MAPK1, MAPK3, VEGF, and MMP-2 in ERBB2 shRNA group decreased significantly, TIMP-2 increased markedly, and proliferation, invasion, and migration abilities of cells decreased markedly after transfection, showing statistically significant differences (All p < 0.05). By contrast, the expression levels of ERBB2, MAPK1, MAPK3, VEGF, and MMP-2 increased remarkably in ERBB2 group, while TIMP-2 decreased significantly, and cell proliferation, invasion, and migration ability increased evidently after transfection, with statistically significant differences (All p < 0.05). CONCLUSIONS: Silencing ERBB2 gene expression may inhibit the activation of MAPK1/MAPK3 signaling pathway and thus suppress the proliferation, invasion, and migration of ovarian cancer cells. Overexpression of ERBB2 gene can reverse those trends, which in turn support the role of ERBB2 gene expression silencing in molecular targeted therapy of ovarian cancer.


Asunto(s)
Movimiento Celular , Silenciador del Gen , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Receptor ErbB-2/genética , Transducción de Señal , Células Cultivadas , Femenino , Humanos , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Invasividad Neoplásica , Receptor ErbB-2/metabolismo , Transducción de Señal/genética
20.
Value Health ; 17(7): A744, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27202688
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