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1.
Genomics ; 115(2): 110554, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36587749

RESUMO

This study aims to explore the role of SKA1 in cancer diagnosis and prognosis and to investigate the mechanism by which SKA1 affects the malignant behaviors of ovarian cancer. Herein, we analyzed the oncogenic role of SKA1 at pan-cancer level by multiple informatics databases and verified the analysis by in vitro experiments. As a result, SKA1 was upregulated across cancers and was related to poor clinical outcome and immune infiltration. Specifically, the constructed nomogram showed superior performance in predicting the prognosis of epithelial ovarian cancer patients. Furthermore, the in vitro experiments revealed that silencing SKA1 significantly inhibited the proliferation, migratory ability and enhanced the cisplatin sensitivity of ovarian cancer cells. Therefore, we explored the oncogenic and potential therapeutic role of SKA1 across cancers through multiple bioinformatic analysis and revealed that SKA1 may promote ovarian cancer progression and chemoresistance to cisplatin by activating the AKT-FOXO3a signaling pathway.


Assuntos
Cisplatino , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Prognóstico , Transdução de Sinais , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo
2.
BMC Med Educ ; 24(1): 321, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515120

RESUMO

BACKGROUND: Narrative Medicine (NM), a contemporary medical concept proposed in the 21st century, emphasizes the use of narrative as a literary form in medicine. This study aims to explore the understanding about NM and willingness to learn NM among medical students in our hospital. METHODS: A questionnaire survey was conducted among 130 students at Xiangya Medical College of Central South University. RESULTS: The findings revealed that a small percentage of students (3.1%) were familiar with narrative medicine and its training methods. Knowledge about the treatment skills (77.7%) and core content (55.4%) of narrative medicine was limited among the students. Despite this, a majority (63.1%) expressed a lack of interest in further understanding and learning about narrative medicine. Surprisingly, the survey indicated that students possessed a high level of narrative literacy, even without formal training in narrative medicine. Additionally, over half of the surveyed students (61.5%) believed that narrative medicine could benefit their clinical practice. CONCLUSIONS: This study serves as a preliminary basis for the future development of narrative medicine education in China. It highlights the need to prioritize medical humanities education and provide medical students with more opportunities to access information on narrative medicine. By doing so, we can strive to enhance the visibility and promote the integration of narrative medicine into medical humanities education in China.


Assuntos
Medicina Clínica , Educação Médica , Medicina Narrativa , Estudantes de Medicina , Humanos , Ciências Humanas/educação , Medicina Clínica/educação
3.
J Acoust Soc Am ; 153(5): 3055, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37219493

RESUMO

Sound field reproduction, which attempts to create a virtual acoustic environment, is a fundamental technology in the achievement of virtual reality. In sound field reproduction, the driving signals of the loudspeakers are calculated by considering the signals collected by the microphones and working environment of the reproduction system. In this paper, an end-to-end reproduction method based on deep learning is proposed. The inputs and outputs of this system are the sound-pressure signals recorded by microphones and the driving signals of loudspeakers, respectively. A convolutional autoencoder network with skip connections in the frequency domain is used. Furthermore, sparse layers are applied to capture the sparse features of the sound field. Simulation results show that the reproduction errors of the proposed method are lower than those generated by the conventional pressure matching and least absolute shrinkage and selection operator methods, especially at high frequencies. Experiments were performed under conditions of single and multiple primary sources. The results in both cases demonstrate that the proposed method achieves better high-frequency performance than the conventional methods.

4.
Sensors (Basel) ; 22(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897996

RESUMO

The core of underwater acoustic recognition is to extract the spectral features of targets. The running speed and track of the targets usually result in a Doppler shift, which poses significant challenges for recognizing targets with different Doppler frequencies. This paper proposes deep learning with a channel attention mechanism approach for underwater acoustic recognition. It is based on three crucial designs. Feature structures can obtain high-dimensional underwater acoustic data. The feature extraction model is the most important. First, we develop a ResNet to extract the deep abstraction spectral features of the targets. Then, the channel attention mechanism is introduced in the camResNet to enhance the energy of stable spectral features of residual convolution. This is conducive to subtly represent the inherent characteristics of the targets. Moreover, a feature classification approach based on one-dimensional convolution is applied to recognize targets. We evaluate our approach on challenging data containing four kinds of underwater acoustic targets with different working conditions. Our experiments show that the proposed approach achieves the best recognition accuracy (98.2%) compared with the other approaches. Moreover, the proposed approach is better than the ResNet with a widely used channel attention mechanism for data with different working conditions.


Assuntos
Aprendizado Profundo , Acústica
5.
BMC Womens Health ; 21(1): 214, 2021 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022866

RESUMO

BACKGROUND: To investigate the clinical efficacy of the MyoSure hysteroscopic tissue removal system in the treatment of endometrial and cervical polyps in women with an intact hymen. METHODS: Retrospective analysis was performed on the clinical data of 32 patients treated with the MyoSure hysteroscopic tissue removal system for endometrial and cervical polyps. RESULTS: All the patients successfully completed the procedure. No intraoperative complications, such as cervical trauma, uterine perforation or TURP syndrome, were reported. The surgical time ranged from 5 to 35 min, with an average time of 19.3 min, and the intraoperative blood loss ranged from 2 to 50 ml with an average blood loss of 10.8 ml. After surgery, all patients were shown to have intact hymens. No residual polyp tissues were observed under the microscope, and abnormal uterine bleeding was relieved. CONCLUSIONS: The MyoSure hysteroscopic tissue removal system can be a safe and effective treatment for endometrial and cervical polyps in women with an intact hymen.


Assuntos
Pólipos , Doenças Uterinas , Neoplasias Uterinas , Feminino , Humanos , Hímen/cirurgia , Histeroscopia , Pólipos/cirurgia , Gravidez , Estudos Retrospectivos
6.
Mol Med ; 26(1): 70, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32640974

RESUMO

BACKGROUND: Ovarian cancer is one of the most common gynecologic cancers and has high mortality rate due to the lack of early diagnosis method and efficient therapeutic agents. circCELSR1 is up-regulated in ovarian cancer, but its role and mechanisms in ovarian cancer are unclear. METHODS: Gene expression of circCELSR1, miR-598 and BRD4 in ovarian cells was examined by qRT-PCR. Protein level was determined by Western blotting. Bioinformatic analysis and luciferase assay determined the molecular binding among circCELSR1, miR-598 and BRD4 3' UTR. Cell proliferation, migration, invasion and apoptosis were determined by colony formation, wound healing assay, transwell assay and flow cytometry analysis, respectively. An abdominal cavity metastasis nude mice model was used to determine the in vivo function of circCELSR1. RESULTS: circCELSR1 and BRD4 were promoted, but miR-598 was suppressed in various ovarian cancer cells. circCELSR1 bound to miR-598 and promoted expression of its downstream target BRD4. Knockdown of circCELSR1 suppressed proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), but promoted apoptosis in ovarian cancer cells, and these effects were reversed by miR-598 inhibition or BRD4 overexpression. circCELSR1 inhibition decreased the expression of BRD4 and its downstream proliferation/migration related genes by targeting miR-598. Furthermore, knockdown of circCELSR1 suppressed ovarian cancer growth and metastasis in nude mice. CONCLUSION: Knockdown of circCELSR1 inhibited BRD4-mediated proliferation/migration related signaling via sponging miR-598, thereby repressing ovarian cancer progression. This study provides a new regulatory mechanism of ovarian cancer may facilitate the development of therapeutic agents for ovarian cancer.


Assuntos
Caderinas/genética , Proteínas de Ciclo Celular/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , RNA Circular , Transdução de Sinais , Fatores de Transcrição/metabolismo , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Ovarianas/patologia , Interferência de RNA
7.
Biotechnol Lett ; 42(6): 1051-1060, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32124141

RESUMO

OBJECTIVES: This study on all-trans retinoic acid was designed to explore its effect on the ability of Fra-1 to cervical cancer cell development. The results show that all-trans retinoic acid enhances the effect of Fra-1 on inhibiting cervical cancer proliferation and the glucose consumption, its effect on the loss of mitochondrial membrane potential, on the decreasing of lactic acid as well as ATP, and also influences the expression of MDM2/P53/P21 and LDHA. RESULTS: The results show that the expression of Fra-1 is higher in all-trans retinoic acid-treated cervical cancer. Flow cytometry and kit detection show that all-trans retinoic acid can enhance the ability of Fra-1 to lose the mitochondrial membrane potential, inhibit the glucose consumption and the production of lactic acid as well as ATP. CCK8 and colony formation assays indicate that all-trans retinoic acid enhances the ability of Fra-1 to inhibit cell proliferation. In addition, through Western blot analysis, it was determined that P53 and P21 were up-regulated, and MDM2 and LDHA were down-regulated. CONCLUSION: The overall results of the study strongly suggest that all-trans retinoic acid enhances the effect of Fra-1 on inhibiting cervical cancer proliferation and metabolism in vitro, and also influences the expression of MDM2/P53/P21 and LDHA.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Tretinoína/farmacologia , Neoplasias do Colo do Útero/metabolismo , Antineoplásicos/farmacologia , Feminino , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos
8.
Int J Gynecol Cancer ; 28(6): 1085-1089, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29727350

RESUMO

Epithelial ovarian cancer (EOC) is the fifth most common cause of cancer mortality among women. At present, EOC is treated with one or in a combination of treatments, commonly debulking surgery, combining a platinum-based and a taxane-based therapy; however, the patients have a risk of injury to the bowel, bladder, ureter, and vessels during surgery and many of them suffer from severe adverse effects caused by chemotherapy. Pharmaceutical inhibition of cyclooxygenase (COX) might be an important therapeutic tool in cancer treatment, as COX contributes to cancer progression by upregulating the levels of downstream metabolites. In this review article, we have discussed the role of COX in cancer progression and the therapeutic use of COX inhibitors in the treatment of EOC with subsequent clinical studies and future management. Usually, gonadotropins can promote prostaglandin E2 production in EOC cells via COX-1 and -2 upregulations through the PI3K/AKT signaling pathway. Several reports have shown that treatment of EOC cells with COX-1- and COX-2-specific inhibitors exhibits a therapeutic effect on EOC both in vitro and in vivo. However, more clinical investigations are needed to develop therapeutic COX inhibitors for the prevention and treatment of EOC without adverse effects.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Animais , Carcinoma Epitelial do Ovário/enzimologia , Feminino , Humanos
9.
J Acoust Soc Am ; 143(5): EL367, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29857735

RESUMO

Uncertain speed of sound will lead that the interval perturbation method fails to precisely predict the uncertain acoustic field in some frequency bands. An uncertainty reduction technique is proposed for this problem. This technique first determines the bands in which the interval method is being invalid through the modal frequency analysis. Then, the dimensionality of the uncertain parameters is reduced by converting the uncertain speed of sound into a certain one. This technique can be used in the interval or subinterval perturbation methods. The numerical example demonstrates that the proposed technique is effective for uncertain acoustic field simulation with interval parameters.

10.
BMC Urol ; 14: 52, 2014 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-24996819

RESUMO

BACKGROUND: The simplified International Index of Erectile Function (IIEF-5) is a convenient, reliable and validated diagnostic tool for erectile dysfunction (ED). However, few studies focused on IIEF-5 in ED patients with different pathophysiological causes. ,We aim to compare the IIEF-5 score among ED patients with specific pathophysiologies in this study. METHODS: The IIEF-5 score of 3,327 ED patients (median age 39 years) was analyzed. The primary causes of ED were determined by comprehensive diagnostic procedures in the urology/andrology clinics in five training hospitals. Patients with uncertain pathophysiologic cause were excluded. RESULTS: 176 patients were excluded, 3151 patients with ED history between 0.5 year and 20 years, were enrolled. The causes of ED was classified as psychogenic (59.2%), vasoculogenic (21.3%), neurogenic (4.1%), anatomical/structural (2.8%), hormonal (7.1%) or drug-induced (5.5%). A significant difference was detected in the median IIEF-5 score between psychogenic ED and organic ED (15 (IQR 13, 17) versus 12 (IQR 9.5, 14.5), P < 0.001). There was no significant difference of IIEF-5 scores among the organic groups (P = 0.073), or between arteriogenic and venogenic groups (13 (IQR 10.5, 15.5) versus 13 (IQR 11-15), P = 0.912 (adjusted α = 0.017)). However, the median IIEF-5 score of those with a mixed vascular cause was the lowest among vasculogenic patients (11 (IQR 8.5-13.5), scores for the three groups: P = 0.003.). CONCLUSIONS: The IIEF-5 scores of men with psychological ED are higher than those with organic causes, but there is no difference among patients with different organic pathophysiologies. Our data indicate that IIEF-5 is not a definitive diagnostic tool to discriminate the pathophysiological causes of ED.


Assuntos
Disfunção Erétil/diagnóstico , Inquéritos e Questionários , Adulto , Distribuição por Idade , Idoso , Disfunção Erétil/etiologia , Disfunção Erétil/fisiopatologia , Disfunção Erétil/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
11.
JASA Express Lett ; 4(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717470

RESUMO

Predicting acoustic transmission loss in the SOFAR channel faces challenges, such as excessively complex algorithms and computationally intensive calculations in classical methods. To address these challenges, a deep learning-based underwater acoustic transmission loss prediction method is proposed. By properly training a U-net-type convolutional neural network, the method can provide an accurate mapping between ray trajectories and the transmission loss over the problem domain. Verifications are performed in a SOFAR channel with Munk's sound speed profile. The results suggest that the method has potential to be used as a fast predicting model without sacrificing accuracy.

12.
Med Educ Online ; 28(1): 2258000, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37722672

RESUMO

Objective: To explore the effect on empathy skills of integrating narrative medicine instruction into clinical internship undergraduate medical education.Methods: One hundred clinical undergraduate students who were transferred to gynecology and obstetrics in 2016 were selected as subjects and divided into two groups. The control group adopted the traditional practice teaching mode, while the experimental group adopted a narrative medicine integrated with traditional teaching mode. The impact of the narrative medicine course was evaluated using the Davis Empathy Scale, and the students' acceptance of the course was investigated using a self-developed questionnaire.Results: After completion of the rotation, the empathy scores of the experimental group were higher than those of the control group (p < 0.05). Students in the experimental group rated the integration of narrative medicine into the internship class highly, and most students thought that the narrative medicine course was of great benefit with respect to the humanistic quality of medical teaching.Conclusion: The application of narrative medicine teaching in the clinical practice teaching of obstetrics and gynecology promoted students to improve their empathy ability.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Internato e Residência , Medicina Narrativa , Feminino , Gravidez , Humanos , Estudantes
13.
ACS Biomater Sci Eng ; 9(1): 153-164, 2023 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-36571764

RESUMO

Fe has immense potential for biodegradable orthopedic applications, but it degrades slowly in the physiological environment. Inducing galvanic couple by alloying Cu to Fe using ball milling is a promising approach. However, the ductile nature of Cu leads to the cold welding of a large amount of Cu powder during ball milling, which makes it difficult to disperse uniformly in the Fe matrix. Here, a Fe-CuO implant with highly dispersed Cu particles in the matrix was developed by shift-speed ball milling and selective laser melting. Specifically, copper oxide (CuO) particles were selected as precursors and dispersed in Fe powders by ball milling since they were brittle and would not be cold-welded during ball milling. After further milling in higher energy, it was found that CuO particles reacted with Fe and generated Cu particles through a stress-activated redox reaction. Subsequently, the obtained powders were prepared into a Fe-CuO implant using selective laser melting. Microstructure examination revealed that the Cu phases in the implant were dispersed evenly in the Fe matrix, which was considered to establish a large number of galvanic couples and aggravated the galvanic corrosion tendency. Electrochemical tests indicated that the implant had improved performance in degradation behavior in terms of high corrosion current density (22.4 µA/cm2), low corrosion resistance (1319 Ω cm2), and good degradation stability. In addition, it presented antibacterial effects against Escherichia coli and Staphylococcus aureus by diffusion mechanisms with killing rates of 90.7 and 96.7%, respectively, as well as good cytocompatibility.


Assuntos
Próteses e Implantes , Estresse Mecânico , Corrosão , Oxirredução
14.
Int J Gynaecol Obstet ; 163(1): 115-122, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37211662

RESUMO

OBJECTIVE: To compare and analyze the clinical efficacy and reproductive outcomes of the hysteroscopic tissue removal system (MyoSure) and hysteroscopic electroresection in the treatment of benign intrauterine lesions in women of reproductive age. METHODS: This is a retrospective study of patients with benign intrauterine lesions treated with MyoSure or hysteroscopic electroresection. The primary outcomes were operative time and resection completeness, and reproductive outcomes were followed up and compared. Secondary outcomes included perioperative adverse events and postoperative adhesions seen during second-look hysteroscopy. Data analysis was performed using χ2 and Fisher tests for qualitative variables and Student t-test for quantitative variables. RESULTS: The operative times of patients with type 0 or I myoma, endometrial polyps, or retained products of conception in the MyoSure group were shorter than those in the electroresection group but were not significantly different for patients with type II myomas. The complete resection rate was lower in the MyoSure group than in the electroresection group. The degree of decrease in the American Fertility Society score of intrauterine adhesion in the MyoSure group was significantly higher (2.90 ± 1.29 points vs 1.31 ± 0.89 points, P = 0.025). The time to pregnancy and the pregnancy rate were higher in the MyoSure group (13.14 ± 7.85 months vs 16.26 ± 8.22 months, P = 0.040; 65.12% vs 54.55%, P = 0.045), but there was no significant difference in the term live birth rate, premature birth rate, or abortion rate between the two groups. CONCLUSION: MyoSure has advantages of a shortened operative time and improvement in reproductive outcomes such as pregnancy rate. However, for type II myomas, MyoSure has limitations, and a comprehensive evaluation before the procedure is required.


Assuntos
Leiomioma , Mioma , Doenças Uterinas , Gravidez , Humanos , Feminino , Leiomioma/cirurgia , Leiomioma/patologia , Estudos Retrospectivos , Doenças Uterinas/cirurgia , Histeroscopia/métodos , Resultado do Tratamento , Mioma/etiologia
15.
Front Immunol ; 13: 925618, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898502

RESUMO

Aims: Cuproptosis is a recently identified form of programmed cell death; however, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: A set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ferredoxin 1 (FDX1), the key regulator of cuproptosis. A cuproptosis-related risk score (CRRS) was developed via correlation analyses, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression. The metabolic features, mutation signatures, and immune profile of CRRS-classified HCC patients were investigated, and the role of CRRS in therapy guidance was analyzed. Results: FDX1 was significantly downregulated in HCC, and its high expression was associated with longer survival time. HCC patients in the high-CRRS group showed a significantly lower overall survival (OS) and enriched in cancer-related pathways. Mutation analyses revealed that the high-CRRS HCC patients had a high mutational frequency of some tumor suppressors such as tumor protein P53 (TP53) and Breast-cancer susceptibility gene 1 (BRCA1)-associated protein 1 (BAP1) and a low frequency of catenin beta 1 (CTNNB1). Besides, HCC patients with high CRRS showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve (AUC) values of CRRS in predicting the efficiency of sorafenib and the non-responsiveness to transcatheter arterial chemoembolization (TACE) in HCC patients reached 0.877 and 0.764, respectively. Significance: The cuproptosis-related signature is helpful in prognostic prediction and in guiding treatment for HCC patients.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Prognóstico , Fatores de Risco , Microambiente Tumoral/genética , Cobre , Apoptose
16.
Kaohsiung J Med Sci ; 38(11): 1070-1079, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36098468

RESUMO

Bladder cancer (BC) is a familiar malignancy with high morbidity and mortality. The effect of treatment is unsatisfactory after the metastasis and invasion of BC. Hence, more studies should be carried out to explore the metastasis of BC. RT-qPCR or/and western blot was conducted to evaluate miR-494-3p, KLF9, and RGS2 expression. Cell proliferation and invasion were estimated by MTT assay and transwell assay, respectively. Cell migration was tested by wound healing assay and transwell assay. Dual-luciferase reporter gene assay was employed to validate the interplay between miR-494-3p and KLF9 mRNA. The interaction between KLF9 and RGS2 promoter was verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. miR-494-3p expression was upregulated, whereas KLF9 and RGS2 were downregulated in BC cells. miR-494-3p inhibition was competent to limit the growth of BC cells. KLF9 knockdown abolished the miR-494-3p depletion-mediated inhibitory growth of BC cells. Mechanistically, we found that KLF9 was a downstream gene of miR-494-3p and could bind to the promoter region of RGS2 to promote the expression of RGS2. Moreover, RGS2 knockdown abrogated the suppressive effects of miR-494-3p knockdown on the proliferation, migration, and invasion of BC cells. Notably, miR-494-3p inhibition obstructed the tumor growth in nude mice. miR-494-3p silencing inhibited the progression of BC by regulating the KLF9/RGS2 axis in vitro and in vivo, which laid the foundation for experiments of miR-494-3p in BC and provided therapeutic targets for BC.


Assuntos
MicroRNAs , Neoplasias da Bexiga Urinária , Camundongos , Animais , Neoplasias da Bexiga Urinária/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética
17.
Front Genet ; 12: 693259, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512721

RESUMO

Ovarian cancer is one of the most common gynecological malignancies with highest mortality rate among all gynecological malignant tumors. Advanced ovarian cancer patients can obtain a survival benefit from chemotherapy, including platinum drugs and paclitaxel. In more recent years, the administration of poly-ADP ribose polymerase inhibitor to patients with BRCA mutations has significantly improved the progression-free survival of ovarian cancer patients. Nevertheless, primary drug resistance or the acquisition of drug resistance eventually leads to treatment failure and poor outcomes for ovarian cancer patients. The mechanism underlying drug resistance in ovarian cancer is complex and has not been fully elucidated. Interestingly, different non-coding RNAs (ncRNAs), such as circular RNAs, long non-coding RNAs and microRNAs, play a critical role in the development of ovarian cancer. Accumulating evidence has indicated that ncRNAs have important regulatory roles in ovarian cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically highlight the emerging roles and the regulatory mechanisms by which ncRNAs affect ovarian cancer chemoresistance. Additionally, we suggest that ncRNAs can be considered as potential diagnostic and prognostic biomarkers as well as novel therapeutic targets for ovarian cancer.

18.
Cancer Med ; 8(16): 7074-7085, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31568657

RESUMO

OBJECTIVE: Epithelial ovarian cancer (EOC) is a common gynecologic malignancy characterized by extensive peritoneal metastasis and high mortality rate. ABHD11 Antisense RNA1 (ABHD11-AS1) has recently been identified as a regulator of growth and metastasis in multiple tumors, including EOC. However, the biological function and potential mechanism of ABHD11-AS1 in EOC remains poorly understood. METHODS: Immunohistochemistry, western blot, and qRT-PCR analysis were used to determine the expression pattern of ABHD11-AS1 and epidermal growth factor receptor (EGFR) in both EOC tissues and cell lines, respectively. Colony formation, transwell and wound healing assays were performed to evaluate the roles of EGFR and ABHD11-AS1 on the capacity of cell proliferation, migration, and invasion. Western blot analysis was performed to measure the regulation of EGFR pathway on STAT3. Moreover, chromatin immunoprecipitation was employed to demonstrate the interaction between ABHD11-AS1 and STAT3. RNA immunoprecipitation was subjected to prove the direct binding between ABHD11-AS1 and EZH2. Immunofluorescence staining was performed to measure the expression and localization of TIMP2. EOC mouse model was conducted for validating the role of ABHD11-AS1 in vivo. RESULTS: EGFR and ABHD11-AS1 were highly expressed in EOC tissues and cell lines. Knockdown of EGFR or ABHD11-AS1 inhibited cell growth, migration, and invasion of EOC cells. Expression of ABHD11-AS1 was regulated by the activation of EGFR signaling pathway, mediated by STAT3. Besides, ABHD11-AS1 was shown to silence TIMP2 by binding to chromatin-modifying enzyme EZH2. Furthermore, inhibition of EGFR pathway or ABHD11-AS1 repressed the tumor growth of EOC. CONCLUSION: We defined the regulatory relationship between the EGFR signaling pathway, ABHD11-AS1, EZH2, and TIMP2 suggesting that ABHD11-AS1 may act as an oncogene and a potential target for antitumor therapies in ovarian cancer.


Assuntos
Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Feminino , Humanos , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais
19.
Cancer Biol Ther ; 20(7): 956-966, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31062668

RESUMO

Background: Ovarian cancer (OC) is the gynecologic malignant tumor with high mortality. Accumulating evidence indicates that M2-like tumor-associated macrophages (TAMs) can secret EGF to participate in ovarian cancer growth, migration, and metastasis. An EGF-downregulated lncRNA, LIMT (lncRNA inhibiting metastasis), was identified as a critical regulator of mammary cell migration and invasion. Nevertheless, whether EGF secreted from M2-like TAMs regulates LIMT expression in ovarian cancer progression remains largely unknown. Methods: The human OC cell lines OV90 and OVCA429 were recruited in this study. The differentiation of the human monocyte cell line THP-1 into M2-like TAMs was confirmed using flow cytometry within the application of phorbol 12-myristate 13-acetate (PMA). ELISA was performed to detect EGF concentration in co-culture system of M2-like TAMs and OC cell lines. Moreover, CCK-8, flow cytometry and immunofluorescence staining of Ki67 were performed to assess the capacity of cell proliferation. Besides, cell migration and invasion were determined by wound healing and transwell assays. Furthermore, the expression levels of epithelial-mesenchymal transition (EMT) markers and EGFR/ERK signals were analyzed by qRT-PCR and western blot. Female athymic nude mice (8-12 weeks of age; n = 8 for each group) were recruited for in vivo study. Results: In the present study, THP-1 cells exhibited the phenotype markers of M2-like TAMs with low proportion of CD14+ marker and high proportion of CD68+, CD204+, CD206+ markers within the application of PMA. After co-culturing with M2-like TAMs, EGF concentration in the supernatants was significantly increased in a time-dependent manner. Besides, OC cells presented better cell viability, higher cell proliferation, and stronger migration and invasion. The expression of EMT-related markers N-cadherin, Vimentin and EGFR/ERK signals were markedly up-regulated, while E-cadherin was significantly decreased. However, these effects induced by co-culture system were reversed by the application of AG1478 (an EGFR inhibitor) or LIMT overexpression. Furthermore, the endogenous expression of LIMT was decreased in OC cell lines compared with the control group. Also, the in vivo experiments verified that the inhibition of EGFR signaling by AG1478 or overexpression of LIMT effectively repressed the tumor growth. Conclusion: Taken together, we demonstrated that EGF secreted by M2-like TAMs might suppress LIMT expression via activating EGFR-ERK signaling pathway to promote the progression of OC.


Assuntos
Carcinoma Epitelial do Ovário/etiologia , Carcinoma Epitelial do Ovário/metabolismo , Fator de Crescimento Epidérmico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Macrófagos/metabolismo , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/genética , Animais , Biomarcadores Tumorais , Carcinoma Epitelial do Ovário/patologia , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular , Transformação Celular Neoplásica , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem , Macrófagos/imunologia , Neoplasias Ovarianas/patologia , Transdução de Sinais , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
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