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1.
Genomics ; 115(2): 110554, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36587749

RESUMEN

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.


Asunto(s)
Cisplatino , Neoplasias Ováricas , Humanos , Femenino , Cisplatino/farmacología , Cisplatino/uso terapéutico , Pronóstico , Transducción de Señal , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo
2.
BMC Med Educ ; 24(1): 321, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515120

RESUMEN

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.


Asunto(s)
Medicina Clínica , Educación Médica , Medicina Narrativa , Estudiantes de Medicina , Humanos , Humanidades/educación , Medicina Clínica/educación
3.
Acta Pharmacol Sin ; 42(7): 1180-1189, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33149145

RESUMEN

Anexelekto (AXL), a member of the TYRO3-AXL-MER (TAM) family of receptor tyrosine kinases (RTK), is overexpressed in varieties of tumor tissues and promotes tumor development by regulating cell proliferation, migration and invasion. In this study, we investigated the role of AXL in regulating glycolysis in human ovarian cancer (OvCa) cells. We showed that the expression of AXL mRNA and protein was significantly higher in OvCa tissue than that in normal ovarian epithelial tissue. In human OvCa cell lines suppression of AXL significantly inhibited cell proliferation, and increased the sensitivity of OvCa cells to cisplatin, which also proved by nude mice tumor formation experiment. KEGG analysis showed that AXL was significantly enriched in the glycolysis pathways of cancer. Changes in AXL expression in OvCa cells affect tumor glycolysis. We demonstrated that the promotion effect of AXL on glycolysis was mediated by phosphorylating the M2 isoform of pyruvate kinase (PKM2) at Y105. AXL expression was significantly higher in cisplatin-resistant OvCa cells A2780/DDP compared with the parental A2780 cells. Inhibition of AXL decreased the level of glycolysis in A2780/DDP cells, and increased the cytotoxicity of cisplatin against A2780/DDP cells, suggesting that AXL-mediated glycolysis was associated with cisplatin resistance in OvCa. In conclusion, this study demonstrates for the first time that AXL is involved in the regulation of the Warburg effect. Our results not only highlight the clinical value of targeting AXL, but also provide theoretical basis for the combination of AXL inhibitor and cisplatin in the treatment of OvCa.


Asunto(s)
Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Glucólisis/fisiología , Neoplasias Ováricas/tratamiento farmacológico , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Animales , Antineoplásicos/farmacología , Benzocicloheptenos/farmacología , Benzocicloheptenos/uso terapéutico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Desoxiglucosa/farmacología , Desoxiglucosa/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Glucólisis/efectos de los fármacos , Células HEK293 , Humanos , Ratones Desnudos , Neoplasias Ováricas/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Triazoles/farmacología , Triazoles/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Tirosina Quinasa del Receptor Axl
4.
Int J Med Sci ; 18(4): 1030-1038, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33456361

RESUMEN

Previous studies have found that LPS and FRA1 play opposite roles in cervical cancer. In addition, LPS functions by regulating the expression of FRA1 in many disease models, but there is currently no study of their relationship in the energy metabolism of tumor cells. This study, therefore, investigates the effects of LPS on FRA1-mediated glucose metabolism and the possible mechanisms it may have in cervical cancer cells. We constructed FRA1 stable overexpressing/ empty vector cervical cancer cell lines, where glucose consumption, the level of lactic acid production and the expression of energy metabolism related molecules were detected under the stimulation of LPS. At the same time, the changes in proliferation ability of cervical cancer cells were detected. We discovered that LPS promotes glucose consumption, lactic acid production, pentose phosphate bypass, and inhibits aerobic oxidation, by inhibiting the expression of FRA1; and that LPS promotes the growth of cervical cancer cells. Our results indicate that LPS affects the proliferation and glucose metabolism of cervical cancer cells through the FRA1/MDM2/p53 pathway.


Asunto(s)
Cuello del Útero/patología , Lipopolisacáridos/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Neoplasias del Cuello Uterino/genética , Efecto Warburg en Oncología , Carcinogénesis/genética , Carcinogénesis/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Glucosa/metabolismo , Humanos , Ácido Láctico/metabolismo , Vía de Pentosa Fosfato/genética , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Transducción de Señal/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología
5.
BMC Womens Health ; 21(1): 214, 2021 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-34022866

RESUMEN

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.


Asunto(s)
Pólipos , Enfermedades Uterinas , Neoplasias Uterinas , Femenino , Humanos , Himen/cirugía , Histeroscopía , Pólipos/cirugía , Embarazo , Estudios Retrospectivos
6.
Mol Med ; 26(1): 70, 2020 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-32640974

RESUMEN

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.


Asunto(s)
Cadherinas/genética , Proteínas de Ciclo Celular/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , ARN Circular , Transducción de Señal , Factores de Transcripción/metabolismo , Animales , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Modelos Animales de Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Neoplasias Ováricas/patología , Interferencia de ARN
7.
Cancer Cell Int ; 20: 267, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32595416

RESUMEN

BACKGROUND: Alpha protein kinase 2 (ALPK2) was known to play a vital role in cancer by regulating cell cycle and DNA repair. Ovarian cancer (OC) is one of the most lethal malignancies in the female reproductive system. The emphasis of this study is to explore the role of ALPK2 in OC. METHODS: Firstly, tumor and normal tissues were collected for detecting expression of ALPK2 in OC. Lentivirus-mediated shRNA knockdown of ALPK2 was used to construct OC cell model, which was verified by qRT-PCR and Western blot. The cell proliferation was detected by MTT, cell cycle and apoptosis were measured through flow cytometry. Wound-healing assay was conducted to detect the migration of OC cells. RESULTS: It was proved that the expression of ALPK2 in OC tissues was significantly higher than that in normal ovarian tissues. Moreover, knockdown of ALPK2 could inhibit proliferation, migration and promote apoptosis, arrested cell cycle of OC cells. It was also found that ALPK2 knockdown inhibited tumor growth in xenograft mice in vivo. Furthermore, ALPK2 was involved in OC cells via regulating EMT-related proteins (N-cadherin, Vimentin and Snail), inhibiting apoptosis-related proteins (Bcl-2, Bcl-w, HSP27, HSP60, IGF-I, IGF-1sR, Survivin and XIAP), as well as the regulation of downstream pathways (Akt, p-Akt, Cyclin D1, CDK6 and PIK3CA). CONCLUSIONS: In conclusion, ALPK2 might serve as an optional target for prognosis and therapeutic of OC patients.

8.
Mol Biol Rep ; 47(1): 737-752, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31612408

RESUMEN

AP-1 is a dimeric complex that is composed of JUN, FOS, ATF and MAF protein families. FOS-related antigen 1 (FRA1) which encoded by FOSL1 gene, belongs to the FOS protein family, and mainly forms an AP-1 complex with the protein of the JUN family to exert an effect. Regulation of FRA1 occurs at levels of transcription and post-translational modification, and phosphorylation is the major post-translational modification. FRA1 is mainly regulated by the mitogen-activated protein kinases signaling pathway and is degraded by ubiquitin-independent proteasomes. FRA1 can affect biological functions, such as tumor proliferation, differentiation, invasion and apoptosis. Studies have demonstrated that FRA1 is abnormally expressed in many tumors and plays a relevant role, but the specific condition varies from the target organs. FRA1 is overexpressed in breast cancer, lung cancer, colorectal cancer, prostate cancer, nasopharyngeal cancer, thyroid cancer and other tumors. However, the expression of FRA1 is decreased in cervical cancer, and the expression of FRA1 in ovarian cancer and oral squamous cell carcinoma is still controversial. In this review, we present a detailed description of the regulatory factors and functions of FRA1, also, the expression of FRA1 in various tumors and its function in relative tumor.


Asunto(s)
Neoplasias , Proteínas Proto-Oncogénicas c-fos , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , MicroARNs , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/fisiopatología , Factor de Transcripción AP-1
9.
J Minim Invasive Gynecol ; 27(1): 54-59, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30880159

RESUMEN

STUDY OBJECTIVE: To identify factors that affect reproductive outcomes after hysteroscopic adhesiolysis in patients with severe intrauterine adhesions (IUAs, scored between 9 and 12 according to the American Fertility Society classification) and amenorrhea. DESIGN: A retrospective cohort study. SETTING: A university-affiliated hospital. PATIENTS: One hundred fifty-one patients with severe IUAs and amenorrhea. INTERVENTION: Patients were diagnosed via hysteroscopy and underwent at least 1 hysteroscopic adhesiolysis between May 2012 and January 2016. MEASUREMENTS AND MAIN RESULTS: Of 151 patients, 12 were lost to follow-up, and 139 were included in the study with a follow-up period ranging from 2 to 6 years. Of the 139 evaluable patients, 107 (77%) recovered with a normal uterine cavity (free of IUAs), 28 (20.1%) had improved uterine cavity (fewer IUAs), and 4 (2.9%) showed no improvement. Moreover, 79 patients (56.8%) recovered with normal menstruation, 54 (38.9%) showed increased frequency of menstruation, and 6 (4.3%) had persistent amenorrhea. Seventy-seven (55.4%) became pregnant, of whom 13 had a spontaneous miscarriage, 11 birthed prematurely (at 31-36 gestational weeks), 44 experienced term delivery, and 9 were still pregnant at the end of the study. Age >32 years (p = .002, odds ratio [OR] = 3.442), >2 surgeries (p = .027, OR = 2.969), cervical canal adhesions (p = .047, OR = 2.112), and disease course >6 months (p = .037, OR = 2.335) were risk factors for infertility in patients with severe IUAs and amenorrhea. CONCLUSION: Younger age, earlier treatment within the disease course, fewer cervical canal adhesions, and fewer surgical procedures improve the reproductive outcome in patients with severe IUAs and amenorrhea.


Asunto(s)
Amenorrea/cirugía , Histeroscopía/métodos , Infertilidad Femenina/etiología , Adherencias Tisulares/cirugía , Enfermedades Uterinas/cirugía , Adulto , Amenorrea/epidemiología , Amenorrea/etiología , Estudios de Cohortes , Disección/métodos , Femenino , Humanos , Histeroscopía/efectos adversos , Histeroscopía/rehabilitación , Histeroscopía/estadística & datos numéricos , Infertilidad Femenina/epidemiología , Menstruación/fisiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/cirugía , Estudios Retrospectivos , Factores de Riesgo , Adherencias Tisulares/complicaciones , Adherencias Tisulares/epidemiología , Resultado del Tratamiento , Enfermedades Uterinas/complicaciones , Enfermedades Uterinas/epidemiología , Adulto Joven
10.
Biotechnol Lett ; 42(6): 1051-1060, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32124141

RESUMEN

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.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Tretinoina/farmacología , Neoplasias del Cuello Uterino/metabolismo , Antineoplásicos/farmacología , Femenino , Células HeLa , Humanos , Transducción de Señal/efectos de los fármacos
11.
J Perinat Med ; 48(8): 803-810, 2020 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-32769225

RESUMEN

Objectives Post-cesarean section scar diverticulum (PCSD) is a long-term sequela of cesarean section (CS). The aim of this study was to evaluate the clinical utility of PCSD scoring criteria, and also retrospectively investigate the efficacy and fertility of two different surgical methods in 304 patients with PCSD. Methods A total of 304 PCSD patients who underwent hysteroscopy or combined hysteroscopy and laparoscopy (referred to as laparoscopy) in our hospital from 2016 to 2018 were retrospectively analyzed. Preoperative condition was analyzed by the PCSD scoring criteria and its influencing factors were explored. The efficacy, its influencing factors and pregnancy success rate of the two different surgical methods on PCSD was also analyzed after 6- and 12-months follow-up. Results PCSD was more severe (high score) in patients who experienced caesarean section with one of the following conditions: age >30 years old, without medical indications or retroflexed uterus. The postoperative efficacy of patients subjected to hysteroscopy or laparoscopy was 81.25 and 89.47% (after 6 months), and 79.53 and 87.50% (after 12 months), respectively. Hysteroscopic surgery was better for PCSD patients who had fewer CS and thicker residual muscle layer and worse for PCSD patients with a longer distance of incision defect to the end of the cervix. Postoperative fertilization showed that pregnancy success rate of patients subjected to hysteroscopy or laparoscopy was 56.2 and 50%, respectively. Conclusions The PCSD scoring is an effective method for assessing the severity of PCSD, and hysteroscopy and laparoscopy are effective modalities for PCSD. Hysteroscopy is also an option for patients with fertility needs.


Asunto(s)
Cesárea , Cicatriz , Divertículo , Histeroscopía , Laparoscopía , Adulto , Factores de Edad , Causalidad , Cesárea/efectos adversos , Cesárea/métodos , China , Cicatriz/diagnóstico , Cicatriz/epidemiología , Cicatriz/etiología , Cicatriz/cirugía , Divertículo/diagnóstico , Divertículo/epidemiología , Divertículo/etiología , Divertículo/cirugía , Femenino , Preservación de la Fertilidad/métodos , Preservación de la Fertilidad/estadística & datos numéricos , Humanos , Histeroscopía/efectos adversos , Histeroscopía/métodos , Laparoscopía/efectos adversos , Laparoscopía/métodos , Efectos Adversos a Largo Plazo , Embarazo , Periodo Preoperatorio , Índice de Severidad de la Enfermedad
12.
Arch Gynecol Obstet ; 302(5): 1215-1220, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32803393

RESUMEN

OBJECTIVE: To investigate the effect of hysteroscopic surgery on the outcomes of obstetrics and gynecology among patients with cesarean section diverticulum. METHODS: Ninety-nine infertile patients with cesarean section diverticulum received hysteroscopic treatment and were retrospectively analyzed. Patients were followed for 1 year. RESULTS: The study included ninety-nine symptomatic patients with cesarean section diverticulum. After surgery, the menstrual periods of patients were improved from 11.15 ± 4.44 to 7.69 ± 2.85 days. Forty-seven (47/99) women became pregnant after surgery. The number of patients who became pregnant with an anteflexion uterus after hysteroscopic surgery is 32 (32/57), and the number of women who became pregnant with a retroflexion uterus is 15 (15/42). CONCLUSION: Hysteroscopic surgery could improve the PCSD-associated prolonged menstrual bleeding, and satisfactory obstetrical outcomes could be achieved by the surgery treatment in women with cesarean defect.


Asunto(s)
Cesárea/efectos adversos , Cicatriz/etiología , Cicatriz/cirugía , Divertículo/cirugía , Histeroscopía/métodos , Hemorragia Uterina/cirugía , Adulto , Cicatriz/patología , Femenino , Humanos , Histeroscopía/efectos adversos , Infertilidad Femenina/etiología , Infertilidad Femenina/cirugía , Embarazo , Estudios Retrospectivos , Resultado del Tratamiento , Hemorragia Uterina/etiología
13.
J Cell Biochem ; 120(3): 2940-2953, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30537410

RESUMEN

Cisplatin (DDP)-based chemotherapy is a standard strategy for ovarian cancer (OC), while chemoresistance remains a major therapeutic challenge. Transcription factor SOX9 has been reported to be associated with tumor cell proliferation, metastasis, and chemoresistance. In the current study, we observed a higher SOX9 expression in OC cell lines; SOX9 overexpression might aggravate the chemoresistance of the OC cell to DDP, whereas its knockdown enhanced the chemoresistance. We screened for candidate microRNAs (miRNAs) which might target SOX9 using online tools and further verified the effect of miR-34c, one of the candidate miRNA that significantly inhibited SOX9 expression, in the regulation of OC cell proliferation and chemoresistance to DDP. Further, we verified the interaction between SOX9 and miR-34c, as well as the involvement of ß-catenin signaling in this process. Through the analysis of the correlation between miR-34c expression and the clinical features of patients with OC, we revealed that miR-34c might inhibit OC cell proliferation and chemoresistance to improve the prognosis of patients with OC. Further, the expression of SOX9, ß-catenin, and c-Myc in OC tissues was upregulated and inversely correlated with miR-34c expression, indicating that rescuing miR-34c expression, thus to inhibit SOX9, ß-catenin, and c-Myc expression presents a promising strategy of reducing the chemoresistance of the OC cell to DDP.


Asunto(s)
Resistencia a Antineoplásicos , MicroARNs/genética , Neoplasias Ováricas/genética , Factor de Transcripción SOX9/genética , Factor de Transcripción SOX9/metabolismo , Regiones no Traducidas 3' , Línea Celular Tumoral , Cisplatino , Femenino , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Neoplasias Ováricas/metabolismo , Vía de Señalización Wnt
14.
Gynecol Oncol ; 154(2): 345-353, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31242966

RESUMEN

OBJECTIVE: Cervical HR-HPV persistence is the main risk factor for cervical cancer. We aimed to investigate the association of age and viral factors with HR-HPV persistence. METHODS: From 2010 to 2017, 343,128 women underwent 390,411 tests performed by the Cervista HR-HPV assay (Data C3) and 157,123 women underwent 206,505 tests performed by the GenoArray HR-HPV assay (Data G14) in nine medical centers located in central and eastern China. We combined the test results and identified 9234 HPV-specific baseline-negative records for time-to-event analyses. The study endpoint event was defined as clearance of type/group-specific HPV. Therefore, hazard ratio (HR) < 1 indicated a higher risk of HPV persistence, which is contrary to the common meaning of HR. RESULTS: The median persistence time was 375 and 541.5 days for Data C3 and Data G14, respectively. For every 5-year increase in age, a 15% (95% confidence interval [CI], 11%-19%) decrease in the clearance rate was observed only after 400 days of infection. For each additional co-infected HPV, the HR was 1.80 (95% CI, 1.63-1.97) on infection initiation but decreased by 22% (95% CI, 18%-26%) every 100 days. The HR of infection recurrence was 0.48 (95% CI, 0.32-0.72). The findings were consistent across different populations and test methods and were robust in sensitivity analysis. CONCLUSIONS: We found a time-dependent association of age and viral factors with HPV clearance. Older age reduced HPV clearance only after 400 days of infection. Co-infection promoted HPV clearance in the beginning, but the effect attenuated and reversed as infection persisted. Recurrent same-type infection cleared slower than the previous one.


Asunto(s)
Papillomaviridae/fisiología , Infecciones por Papillomavirus/virología , Adulto , Factores de Edad , Anciano , China , Femenino , Estudios de Seguimiento , Humanos , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Tiempo , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/virología
15.
Acta Pharmacol Sin ; 40(7): 919-928, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30315250

RESUMEN

Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. To gain a better understanding of how traditional Chinese medicine agents exert antitumor effects, we screened 480 natural compounds for their effects on autophagy using a high content screening assay detecting GFP-LC3 puncta in HeLa cells. Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), was identified as a potent activator of autophagy. The activation of autophagy by TBMS1 was evidenced by increased LC3-II amount and GFP-LC3 dots, observation of autophagosomes under electron microscopy, and enhanced autophagic flux. To explore the mechanisms underlying TBMS1-activated autophagy, we performed cheminformatic analyses and surface plasmon resonance (SPR) binding assay that showed a higher likelihood of the binding between Akt protein and TBMS1. In three human breast cancer cell lines, we demonstrated that Akt-mTOR-eEF-2K pathway was involved in TBMS1-induced activation of autophagy, while Akt-mediated downregulations of Mcl-1, Bcl-xl, and Bcl-2 led to the activation of apoptosis of the breast cancer cells. Inhibition of autophagy enhanced the cytotoxic effect of TBMS1 via promoting apoptosis. Our results demonstrate the role and mechanism of TBMS1 in activating autophagy, suggesting that inhibition of cytoprotective autophagy may act as a therapeutic strategy to reinforce the activity of TBMS1 against cancers.


Asunto(s)
Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Saponinas/farmacología , Transducción de Señal/efectos de los fármacos , Triterpenos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo
16.
Med Sci Monit ; 25: 2792-2801, 2019 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-30990212

RESUMEN

BACKGROUND The aim of this study was to investigate the significance of folate receptor-mediated staining solution (FRD) in examination of cervical lesions during gynecological examination. MATERIAL AND METHODS A total of 404 patients participated in this study. FRD staining was applied to screen high grade cervical lesions. ThinPrep cytology test (TCT) and human papillomavirus (HPV) testing were also used for screening high grade cervical lesions. Coincidence rate and KAPPA value of different methods were compared by SPSS software. RESULTS As for CIN2+ and CIN3+, sensitivities for HPV testing were (96.92% and 97.78%) >TCT classification 1 (90.77% and 91.11%) >FRD staining (80.00% and 86.67%) >TCT classification 2 (70.77% and 77.78%), respectively. While specificities for HPV testing were (7.08% and 6.44%)

Asunto(s)
Detección Precoz del Cáncer/métodos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/patología , Células 3T3 , Adulto , Anciano , Animales , Cuello del Útero/patología , Femenino , Receptores de Folato Anclados a GPI/química , Receptores de Folato Anclados a GPI/metabolismo , Ácido Fólico/química , Humanos , Tamizaje Masivo/métodos , Ratones , Persona de Mediana Edad , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/diagnóstico , Sensibilidad y Especificidad , Coloración y Etiquetado/métodos , Neoplasias del Cuello Uterino/diagnóstico , Frotis Vaginal/métodos , Displasia del Cuello del Útero/virología
17.
J Minim Invasive Gynecol ; 26(5): 883-890, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30205163

RESUMEN

STUDY OBJECTIVE: To investigate risk factors for infertility and recurrent cesarean scar pregnancy (CSP) after previous CSP. DESIGN: A retrospective cohort study (Canadian Task Force classification II-1). SETTING: University hospital. PATIENTS: Between January 2007 and April 2016, a total of 650 patients were included, all diagnosed with CSP and treated by high-intensity focused ultrasound (HIFU) and uterine artery embolization (UAE), followed by suction curettage under hysteroscopic guidance. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Follow-up of the reproductive outcomes ended in June 2017. A total of 135 of the 650 patients with CSP were involved in the study, among whom 32 became infertile, 78 had an intrauterine pregnancy, and 25 had recurrent CSP after previous CSP. Age (≥35 years; odds ratio [OR], 4.252; p = .002), ß-human chorionic gonadotropin (≤5000 mIU/mL; OR, 3.778; p = .011), and longer duration of amenorrhea (>56 days; OR, 2.507; p = .05) were risk factors for infertility. Treatment with UAE (OR, 5.796; p = .003), more abortions (≥4; OR, 2.851; p = .022), and being asymptomatic (OR, 4.175; p = .039) were risk factors for recurrent CSP. There was no statistically significant difference in the subsequent outcomes of pregnant women in the HIFU and UAE groups (p >.05). CONCLUSION: More attention should be given to subsequent reproductive outcomes after CSP, not only for intrauterine pregnancy, but also for infertility and recurrent CSP. Early diagnosis and treatment of CSP could reduce the risk of infertility and recurrent CSP. HIFU seemed to be superior to UAE in reducing the risk of recurrent CSP. Patients with CSP should adhere to strict contraception if they do not desire more children.


Asunto(s)
Cesárea/efectos adversos , Cicatriz/cirugía , Ultrasonido Enfocado de Alta Intensidad de Ablación , Embarazo Ectópico/cirugía , Embolización de la Arteria Uterina/efectos adversos , Legrado por Aspiración/efectos adversos , Aborto Inducido/efectos adversos , Aborto Espontáneo/etiología , Adulto , Gonadotropina Coriónica Humana de Subunidad beta , Cicatriz/etiología , Femenino , Estudios de Seguimiento , Humanos , Infertilidad/prevención & control , Embarazo , Resultado del Embarazo , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Arteria Uterina/cirugía , Adulto Joven
18.
Acta Pharmacol Sin ; 39(4): 642-648, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29239350

RESUMEN

Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the molecular mechanisms underlying RA-induced autophagy as well as the relationship between RA-induced autophagy and its cytotoxicity in human breast cancer cells in vitro. Treatment with RA (2-8 µmol/L) dose-dependently enhanced autophagy, as evidenced by increased LC3 levels in breast cancer cell lines T47D, MCF-7 and MDA-MB-231. Furthermore, the Akt-mTOR-eEF-2K signaling pathway was demonstrated to be involved in RA-induced activation of autophagy in the 3 breast cancer cell lines. Treatment with RA (2-10 µmol/L) dose-dependently induced apoptosis in the 3 breast cancer cell lines. Pretreatment with the autophagy inhibitor chloroquine (CQ, 20 µmol/L) significantly enhanced RA-caused cytotoxicity via promoting apoptosis. In conclusion, our results suggest that modulating autophagy can reinforce the cytotoxicity of RA against human breast cancer cells.


Asunto(s)
Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Quinasa del Factor 2 de Elongación/metabolismo , Saponinas/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Cloroquina/farmacología , Regulación hacia Abajo , Femenino , Compuestos Heterocíclicos con 3 Anillos/farmacología , Humanos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(7): 816-820, 2018 Jul 28.
Artículo en Zh | MEDLINE | ID: mdl-30124221

RESUMEN

We reported a case of giant solitary fibrous tumor of vagina and reviewed literature. The clinical features, diagnosis, and treatment schemes for the disease were summarized to improve the understanding of the disease. An elder female patient came to the Third Xiangya Hospital, Central South University, because of abdominal distention and pain for 5 days after menopause for 9 years. The patient was diagnosed as a solitary fibrous tumor of vagina by pathology and immunohistochemistry after complete resection. The tumor size of the patient was the largest according to reported literature, and the tumor recurred 10 months after surgery. The strong positive expression of CD34 and high Ki-67 proliferation index in tumor immunohistochemistry indicate that the prognosis of patients will be poor.


Asunto(s)
Tumores Fibrosos Solitarios/metabolismo , Tumores Fibrosos Solitarios/patología , Carga Tumoral , Neoplasias Vaginales/metabolismo , Neoplasias Vaginales/patología , Anciano , Antígenos CD34/metabolismo , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Pronóstico
20.
Mol Carcinog ; 56(10): 2245-2257, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28544069

RESUMEN

Cervical cancer is one of the most common malignant tumors in women all over the world. The exact mechanism of occurrence and development of cervical cancer has not been fully elucidated. CD38 is a type II transmembrane glycoprotein, which was found to mediate diverse activities, including signal transduction, cell adhesion, and cyclic ADP-ribose synthesis. Here, we reported that CD38 promoted cell proliferation and inhibited cell apoptosis in cervical cancer cells by affecting the mitochondria functions. We established stable cervical cancer cell lines with CD38 over-expressed. CCK8 assay and colony formation assay indicated that CD38 promoted cervical cancer cell proliferation. Nude mouse tumorigenicity assay showed that CD38 significantly promotes tumor growth in vivo. CD38 also induced S phase accumulation in cell cycle analysis and suppressed cell apoptosis in cervical cancer cells. Meanwhile, flow cytometry analysis of mitochondria functions suggested that CD38 decreased intracellular Ca2+ levels in cervical cancer cells and CD38 was involved in down-regulation of ROS levels and prevented mitochondrial apoptosis in cervical cancer cells. The percentage of cells with loss of mitochondrial membrane potential (Δψm) in CD38-overexpressed cervical cancer cells was less than control groups. Furthermore, we found an up-regulation of MDM2, cyclinA1, CDK4, cyclinD1, NF-kB P65, c-rel, and a downregulation of P53, P21, and P38 by Western blot analysis. These results indicated that CD38 enhanced the proliferation and inhibited the apoptosis of cervical cancer cells by affecting the mitochondria functions.


Asunto(s)
ADP-Ribosil Ciclasa 1/metabolismo , Calcio/metabolismo , Glicoproteínas de Membrana/metabolismo , Mitocondrias/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Células HeLa , Humanos , Potencial de la Membrana Mitocondrial , Ratones , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
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