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Arachidonic acid (AA) metabolism plays an important role in vascular homeostasis. We reported that DNA hypomethylation of EPHX2 induced a pro-inflammatory response in vascular endothelial cells (ECs). However, the change in the whole AA metabolism by DNA methylation is still unknown. Using a metabolomic approach, we investigated the effect of DNA methylation on the balance of AA metabolism and the underlying mechanism. ECs were treated with a DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AZA), and AA metabolic profiles were analyzed. Levels of prostaglandin D2 (PGD2) and thromboxane B2 (TXB2), metabolites in the cyclooxygenase (COX) pathway, were significantly increased by 5-AZA treatment in ECs resulting from the induction of PGD2 synthase (PTGDS) and thromboxane A synthase 1 (TBXAS1) expression by DNA hypomethylation. This phenomenon was also observed in liver and kidney cell lines, indicating a universal mechanism. Pathophysiologically, homocysteine, known to cause DNA demethylation, induced a similar pattern of the change of AA metabolism. Furthermore, 5-AZA activated ECs, as evidenced by the upregulation of adhesion molecules. Indomethacin, a COX inhibitor, reversed the effects of 5-AZA on the levels of PGD2 and TXB2, EC activation and monocyte adhesion. In vivo, the plasma levels of PGD2 and TXB2 and the expression of In vivo PTGDS and TBXAS1 as well as adhesion molecules were increased in the aorta of the mice injected with 5-AZA. In conclusion, using a metabolomic approach, our study uncovered that DNA demethylation increased AA metabolites PGD2 and TXB2 by upregulating the expression of the corresponding enzymes, which might contribute to the DNA hypomethylation-induced endothelial activation.
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Ácidos Araquidónicos/metabolismo , Metilación de ADN/fisiología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Animales , Azacitidina/análogos & derivados , Azacitidina/farmacología , Metilación de ADN/efectos de los fármacos , Decitabina , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/fisiología , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Oxidorreductasas Intramoleculares/biosíntesis , Riñón/citología , Riñón/enzimología , Lipocalinas/biosíntesis , Hígado/citología , Hígado/enzimología , Masculino , Metabolómica , Ratones , Tromboxano-A Sintasa/biosíntesisRESUMEN
OBJECTIVE: To determine the ability of contrast-enhanced magnetic resonance imaging to predict myometrial invasion, cervical invasion, and pelvic lymph node metastasis in endometrial carcinoma and to analyze factors that lead to errors in this identification. DESIGN: A retrospective study. SETTING: University general hospital. POPULATION: A total of 167 women diagnosed with endometrial carcinoma. METHODS: All patients received a preoperative contrast-enhanced magnetic resonance imaging scan. Histopathological findings were used as the definitive diagnosis. MAIN OUTCOME MEASURES: The results were compared with histopathological findings, factors that make accurate assessment of myometrial invasion, cervical invasion, and pelvic lymph node metastasis difficult by contrast-enhanced magnetic resonance imaging were analyzed. RESULTS: The sensitivity, specificity, diagnostic accuracy, positive predictive values, and negative predictive values of contrast-enhanced magnetic resonance imaging were 90.9, 91.8, 91.6, 73.2 and 97.6%, respectively, for identifying deep myometrial invasion; 84.2, 96.0, 94.6, 72.7 and 97.9%, respectively, for identifying cervical invasion; and 45.0, 91.2, 85.6, 40.9 and 92.4%, respectively, for identifying pelvic lymph node metastasis. The main causes of error in contrast-enhanced magnetic resonance imaging were myomas, cornual lesions, deep myometrial invasion, large tumor size, non-endometrioid tumor type, and lower tumor grade. CONCLUSION: Contrast-enhanced magnetic resonance imaging has a high accuracy and a low tendency to produce false-negative predictive values. Gynecological oncologists should combine the imaging data and clinical information to make therapeutic decisions and avoid diagnostic errors.
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Carcinoma/secundario , Errores Diagnósticos/prevención & control , Neoplasias Endometriales/patología , Imagen por Resonancia Magnética/métodos , Invasividad Neoplásica/patología , Cuidados Preoperatorios/métodos , Adulto , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Metástasis Linfática/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Medición de RiesgoRESUMEN
Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentially present in mesenchymal cells. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This "paradox" can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.
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Cistadenocarcinoma Seroso/patología , Transición Epitelial-Mesenquimal , MicroARNs/fisiología , Neoplasias Ováricas/patología , Cistadenocarcinoma Seroso/genética , Femenino , Humanos , Neoplasias Ováricas/genéticaRESUMEN
[This corrects the article DOI: 10.3892/ol.2019.10694.].
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Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment, and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.
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Mpox , Humanos , Niño , Mpox/diagnóstico , Mpox/epidemiología , Mpox/prevención & control , Salud Pública , Diagnóstico Diferencial , Vacunación , China/epidemiologíaRESUMEN
OBJECTIVE: To investigate activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in the endometrium of women with polycystic ovary syndrome (PCOS) and its role in endometrium hyperplasia and carcinogenesis, and the factors affecting the activation of the PI3K/Akt pathway. METHODS: From Jan 2007 to Jun 2008, 52 patients with PCOS who underwent dilatation and curettage were selected as experimental group matched with 32 non-PCOS patients as control group. Serous hormonal parameters, fasting blood glucose and insulin, body mass index (BMI), and endometrium pathology were measured and evaluated in all patients. The PCOS patients were divided into insulin resistance and non-insulin resistance group according to homeostasis model assessment-insulin resistance index (HOMA-IR). Meanwhile, the PCOS patients were grouped as normal, endometrial hyperplasia and carcinoma depending on outcome of pathology. The expression of Akt and phosphorylated Akt (p-Akt) were determined by western blot. RESULTS: (1) The expression of p-Akt was significantly higher in PCOS group [(46 ± 18)%] than that in control [(33 ± 9)%, P < 0.01)]. (2) The expression of p-Akt was significantly higher in group of endometrial hyperplasia and carcinoma [(56 ± 19)%] when compared with those in normal endometria group [(31 ± 12)%, P < 0.05]; the expression of p-Akt was significantly higher in group of insulin resistance [(50 ± 19)%] compared with that in non-insulin resistance group [(34 ± 10)%, P < 0.01]. (3) There was a positive correlation between the expression level of p-Akt in endometrium with PCOS and HOMA-IR and BMI respectively (r = 0.400, 0.326, both P < 0.05). CONCLUSIONS: The PI3K/Akt pathway was over activated in endometrium with PCOS which may be associated with the formation of endometrial hyperplasia and carcinoma in PCOS patients. Insulin resistance and obesity may be high risk factors for over-activation of the PI3K/Akt pathway in endometrium with PCOS.
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Endometrio/metabolismo , Resistencia a la Insulina , Fosfatidilinositol 3-Quinasa/metabolismo , Síndrome del Ovario Poliquístico/enzimología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Adulto , Glucemia/metabolismo , Western Blotting , Índice de Masa Corporal , Estudios de Casos y Controles , Hiperplasia Endometrial/sangre , Hiperplasia Endometrial/enzimología , Endometrio/patología , Activación Enzimática , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Insulina/sangre , Hormona Luteinizante/sangre , Síndrome del Ovario Poliquístico/sangre , Factores de RiesgoRESUMEN
OBJECTIVE: To explore the clinical pathological characteristics of Lynch syndrome associated ovarian cancer. METHODS: Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan. 2004 and Jan. 2011, among which 10 patients (LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam II criteria. One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group). RESULTS: Lynch syndrome associated ovarian cancer accounted for 3.8% (10/260), the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7% (10/115). Mean age at time of diagnosis in LS group was (46 ± 7) years, significantly earlier than that in sporadic group [(56 ± 11) years, P < 0.05]. There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics (FIGO) stage (P > 0.05). Most of the tissue differentiation in LS group were well or moderate differentiated, there was statistical difference between the two groups (9/10 vs. 55%, P < 0.05). The 3-year and 5-year survival rate in LS group were 87.5% and 52.5% respectively, compared with 55.4%and 22.7% in sporadic group (all P < 0.05). CONCLUSION: Compared with sporadic ovarian cancer, Lynch syndrome associated ovarian cancer is more likely present as the clinical pathological characteristics of early age of onset, serous adenocarcinoma, lower grade and better prognosis.
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Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Cistadenocarcinoma Seroso/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Ováricas/patología , Adulto , Edad de Inicio , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Epitelial de Ovario , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Cistadenocarcinoma Seroso/epidemiología , Cistadenocarcinoma Seroso/genética , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/epidemiología , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Linaje , Pronóstico , Estudios Retrospectivos , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate clinical characteristics of aerobic vaginitis (AV) and its mixed infections for diagnosis efficiently. METHODS: From April 2008 to December 2008, 516 patients with vaginitis treated in Tianjin Medical University General Hospital were enrolled in this study. AV, bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), trichomonal vaginitis (TV), and cytolytic vaginosis (CV) were diagnosed based on symptoms, sign and vaginal discharge examination. RESULTS: Among 516 cases, AV cases were found in 14.7% (76/516), and AV was common vaginal infection. AV mixed infections was diagnosed in 58% (44/76), including mixed with BV (45%, 20/44), mixed with VVC (30%, 13/44), and mixed with TV (25%, 11/44). Those common symptom of AV were yellow vaginal discharge (63%, 20/32), more vaginal discharge (44%, 14/32). Vaginal pH value was usually more than 4.5 (84%, 27/32). Vaginal cleanliness mainly was grade III - IV (88%, 28/32). Six cases with enterococcus faecium and 4 cases with streptococci were frequently isolated. The symptom and sign of mixed AV infection was atypical. CONCLUSIONS: Aerobic vaginitis is a common lower vaginal infection and easily mixed with other pathogens, especially with BV, VVC or TV. When patients were diagnosed with AV or other vaginal infection, it should be mentioned whether those patients have mixed vaginal infection or AV.
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Coinfección , Vaginitis , Candidiasis Vulvovaginal/microbiología , Femenino , Humanos , Vaginitis por Trichomonas , Vaginitis/tratamiento farmacológico , Vaginosis Bacteriana/microbiologíaRESUMEN
BACKGROUND: A large cervical cyst with a cervical high-grade squamous intraepithelial lesion arising from the cervical stump is rare. After supracervical hysterectomy, there is a risk of various lesions occurring in the cervical stump. We review the types and characteristics of cervical stump lesions and compare total hysterectomy with subtotal hysterectomy. Gynecologists should choose the most suitable surgical method based on both the patient's condition and wishes. If the cervix is retained, patients require a close follow-up. CASE SUMMARY: A 57-year-old woman was admitted to the Gynecology Department for a large pelvic mass. Her chief complaint was abdominal distention for two months. She had undergone subtotal supracervical hysterectomy for leiomyoma 14 years prior. Abdominal ultrasonography detected a 9.1 cm × 8.5 cm × 8.4 cm anechoic mass with silvery fluid in the pelvic cavity and high-risk human papilloma virus 53 (HPV53) was positive. The admission diagnosis we first considered was a pelvic mass mimicking carcinoma of the cervical stump. We performed a laparotomy and a rapid frozen biopsy was suggestive of a fibrous cyst wall coated with a high squamous intraepithelial lesion. The pelvic mass was removed, and a bilateral adnexectomy was implemented. Final pathology confirmed that the pelvic mass was a large inflammatory cyst with a cervical high-grade squamous intraepithelial lesion. After successful intervention, the patient was discharged one week after surgery and there was no recurrence of the vaginal stump at 43 mo. CONCLUSION: When addressing benign uterine diseases, gynecologists should pay adequate attention to retaining the cervix. If the cervix is retained, patients require a close follow-up.
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Cervical cancer is one of the most common malignant neoplasms in gynecology. Protein tyrosine kinase 7 (PTK7) with an inactive kinase domain is an important regulator of multiple Wnt pathways under normal and various pathological conditions and overexpressed in various tumors; however, the clinical and biological significance of PTK7 in cervical cancer is still unknown. In the present study, the protein expression level of PTK7 was detected in clinical cervical cancer patient samples, and the relationship between PTK7 expression and clinicopathological features was analyzed. In addition, the Kaplan-Meier method was performed to estimate the overall survival (OS) and progression-free survival (PFS) of patients to investigate the clinicopathological significance of PTK7 expression. Functional assays demonstrated that knocking down PTK7 might inhibit the ability of cancer cells to proliferate and invade or migrate, both in vivo and in vitro. Thus, PTK7 might serve as a potential target for cervical cancer.
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Biomarcadores de Tumor/genética , Moléculas de Adhesión Celular/genética , Proteínas Tirosina Quinasas Receptoras/genética , Neoplasias del Cuello Uterino/genética , Animales , Biomarcadores de Tumor/metabolismo , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Ratones , Proteínas Tirosina Quinasas Receptoras/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: New-onset systemic lupus erythematosus (SLE) during pregnancy and in the postpartum period is rare, especially when complicated with pre-eclampsia, which is difficult to diagnose accurately. Here, we report a patient with new-onset SLE and antiphospholipid syndrome during pregnancy, which presented as pre-eclampsia at admission. CASE SUMMARY: A 28-year-old primigravid woman was admitted to our hospital in the 27th wk of gestation with the primary diagnosis of severe pre-eclampsia. Although spasmolysis and antihypertensive therapy were administered since admission, the 24-h proteinuria of the 2nd day after admission reached 10311.0 mg. In the 47th h of admission, immunologic examinations revealed increased levels of anti-double stranded DNA antibody, anti-nuclear antibody, anti-cardiolipin antibody, anti-Sjögren's syndrome-related antigen A antibody and anti-nucleosome antibody and decreased levels of complement C3 and C4. One hour later, ultrasonography of the lower limbs showed thrombus of the bilateral popliteal veins. The diagnosis of SLE and antiphospholipid syndrome was indicated. In the 54th h, the patient manifested with convulsion, dyspnea and blurred vision. Ten hours later, intrauterine death was revealed by ultrasonography. Emergent surgery consisting of inferior vena cava filter implantation and subsequent cesarean section was performed. Following glucocorticoid and anticoagulation therapy after delivery, the patient had an optimal response with improvements in symptoms and immunological markers. CONCLUSION: Obstetricians should be aware of the symptoms and immunological examination results to distinguish pre-eclampsia and underlying SLE for optimal pregnancy outcomes.
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The present study focused on exploring the inhibitory mechanism of microRNA (miR)-23a in endometrial cancer. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to investigate miR-23a expression in endometrial tissues and endometrial cancer cells. A colony formation assay using crystal violet staining was performed to compare cell proliferation, while wound-healing and Transwell assays were performed to compare cell migration and invasion. Subsequently, bioinformatics and a luciferase reporter gene assay were used to investigate the effect of miR-23a on sine oculis homeobox homolog 1 (SIX1) expression, and the biological function of SIX1 was analyzed. Additionally, a nude mouse tumorigenicity assay was performed to test the inhibitory effect of miR-23a and Taxol® therapy in endometrial cancer. Finally, immunohistochemistry and RT-qPCR were used to explore the association between miR-23a and SIX1 expression in endometrial cancer tissues. miR-23a was underexpressed in endometrial cancer tissues compared with in para-carcinoma tissues, and the overexpression of miR-23a inhibited proliferation and invasion of endometrial cancer cells. Furthermore, SIX1 was demonstrated to be a downstream target of miR-23a, and miR-23a reduced SIX1 expression. Additionally, SIX1 inversely promoted cell proliferation, migration and invasion. In addition, the effects of reduced cell proliferation and increased cell invasion following miR-23a overexpression could be reversed by adding SIX1 to in vitro culture. Furthermore, the inhibitory effect of miR-23a and Taxol therapy, which reduced SIX1 expression in endometrial cancer, was demonstrated in vivo. Finally, a negative association between miR-23a and SIX1 expression was demonstrated in endometrial cancer tissues. The results of the present study revealed that miR-23a may inhibit endometrial cancer development by targeting SIX1.
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OBJECTIVE: To study clinicopathological characteristics of hereditary nonpolyposis colorectal carcinoma (HNPCC)-associated endometrial carcinoma (EC). METHODS: Totally 421 EC patients admitted to General Hospital of Tianjin Medical University from 1981 to 2006 were divided into three groups: group A: sporadic EC; group B: familial aggregation of EC; group C: HNPCC-associated EC. RESULTS: HNPCC-associated EC accounted for 6.4% (27/421). Mean age at time of diagnosis was 49.7 years in group C, earlier than 56.3 years in group A (P = 0.004) and 55.2 years in group B (P = 0.035). There were 33.3% (9/27) patients with multiple primary carcinomas in group C. It was higher than 14.3% (9/63) in group B and 5.1% (17/331) in group A respectively (P = 0.038, P < 0.01). There was no difference among the three groups in histological type or menopausal status (P > 0.05). The numbers of patients with low grade EC in group C (70.4%, 19/27) and group B (61.35, 38/62) were more than that in Group A (P = 0.013, P = 0.023). Prognosis for group C was better than that in group A (P = 0.021), and 5- and 10-year survival rate in groups A, B and C was 80%, 70%; 88%, 85%; and 96%, 96% respectively. CONCLUSIONS: Mean age at time of diagnosis is earlier in HNPCC-associated EC than that in sporadic EC; patients with HNPCC-associated EC are more frequently complicated with multiple primary carcinomas and of low grade; prognosis is better.
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Adenocarcinoma/patología , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Neoplasias Endometriales/patología , Neoplasias Primarias Múltiples/patología , Adenocarcinoma/epidemiología , Adenocarcinoma/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Múltiples/genética , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. METHODS: Sixty-three endometrial carcinoma (EC) patients, 21 endometrial atypical hyperplasia (AHE) patients and 22 normal control (NE) entered this study. Their clinical information were collected. Fasting serum C-peptide concentration was measured. Expression of IRS-1 in endometrium was examined by RT-PCR and western blot. Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1. RESULTS: C-peptide concentration in EC group was higher than that in NE group [(3.2 +/- 1.1) vs (2.5 +/- 0.7) microg/L, P=0.007]. There were no significant differences in IRS-1 mRNA and protein expression among the three groups. Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. IRS-1 activation in AHE group was also higher than normal control (P=0.045). IRS-1 activation in endometrioid carcinoma [(69 +/- 33) %] was higher than that in other histological types [(34 +/- 31)%; t=2.300, P=0.025]. IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. IRS-1 activation in endometrium was positively correlated with fasting serum C-peptide concentration (r=0.491, P=0.001). CONCLUSIONS: There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia. Activation of IRS-1 in endometrial carcinoma is related with poor clinical-pathologic features and may be a prognostic predictor for this tumor. Over-activation of IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.
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Adenocarcinoma/metabolismo , Neoplasias Endometriales/metabolismo , Endometrio/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Tirosina/metabolismo , Adenocarcinoma/sangre , Adenocarcinoma/patología , Péptido C/sangre , Estudios de Casos y Controles , Hiperplasia Endometrial/sangre , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patología , Neoplasias Endometriales/sangre , Neoplasias Endometriales/patología , Endometrio/patología , Femenino , Humanos , Proteínas Sustrato del Receptor de Insulina/genética , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Fosforilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To study the expression of insulin receptor (INSR) in endometrial cell line Ishikawa3-H-12, and the effects of insulin on proliferation, cell cycle distribution and apoptosis of Ishikawa3-H-12 cells. METHODS: Immunocytochemistry and RT-PCR methods were used to investigate the expression of INSR in Ishikawa3-H-12 cells. The effects of insulin at different concentrations and different time on proliferation, apoptosis and cell cycle distribution of endometrial carcinoma cells were observed by methyl thiazolyl tetrazolium (MTT) assay and fluorescence-activated cell sorting technique. RESULTS: (1) We demonstrated the expression of INSR in Ishikawa3-H-12 cell line. (2) Incubation with insulin stimulated a dose- and time-dependent proliferation response in Ishikawa3-H-12 cells with the peak response occurring at 48 hours with 1 x 10(-4) mol/L insulin incubation [proliferative rate: (340.2 +/- 15.9)%, vs control (100%), P < 0.05]. (3) The percentage of Ishikawa3-H-12 cells at G(0)/G(1) phase decreased and percentage at S phase increased significantly with insulin treatment in a dose- and time-dependent manner with the peak response occurring at 72 hours with 1 x 10(-4) mol/L insulin incubation [G(0)/G(1) phase (27.7 +/- 2.5)%, S phase (55.2 +/- 1.4)%, vs control: (67.6 +/- 1.5)% and (15.7 +/- 1.0)%, P < 0.05], whereas that of G(2)/M phase did not show significant alteration. (4) The apoptosis rate of Ishikawa3-H-12 cells was decreased gradually with increasing concentration of insulin, while the alteration was time-independent. The peak response occurred with 1 x 10(-4) mol/L insulin incubation [apoptosis rate: (1.76 +/- 0.16)%, (1.70 +/- 0.15)%, (1.56 +/- 0.20)%, (1.31 +/- 0.24)% when incubated at 24, 48, 72 and 96 hours respectively, vs control, P < 0.05]. CONCLUSION: Insulin can promote the proliferation and inhibit the apoptosis of endometrial carcinoma cells.
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Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Insulina/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor de Insulina/biosíntesis , Receptor de Insulina/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de TiempoAsunto(s)
Vacunas contra la COVID-19 , COVID-19/prevención & control , COVID-19/epidemiología , Niño , HumanosRESUMEN
The aims of this study are to establish an embryonic stem (ES) cell model of polycystic ovary syndrome and to characterize this ES cell line. ES cells were isolated and cultured from 322 wasted fertilized embryos from polycystic ovary syndrome (PCOS) patients in vitro. They were also characterized by development and differential markers. ES cells from PCOS subject present normal development profile with ES-specific markers such as OCT-4 and SSEA-4. These ES cells can also differentiate into three germ layer derivatives and form teratomas in vivo. ES cells from PCOS patients pose development and differentiation potentials as you would expect of cells from non-PCOS patients; therefore, they can be used as a cellular model to study the pathology of PCOS.
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Células Madre Embrionarias/citología , Síndrome del Ovario Poliquístico/patología , Adulto , Técnicas de Cultivo de Célula , Diferenciación Celular , Femenino , Humanos , CariotipoRESUMEN
BACKGROUND: Cancer-associated fibroblasts (CAFs) are believed to play an essential role in cancer initiation and development. However, little research has been undertaken to evaluate the role of CAFs in endometrial cancer (EC) progression. We aim to detect the functional contributions of CAFs to promote progression of EC. METHODS: Stromal fibroblasts were isolated from endometrioid adenocarcinomas and normal endometrial tissues. The conditioned media of cultured CAFs and normal fibroblasts (NFs) were collected to detect the level of stromal cell-derived factor-1alpha (SDF-1α), macrophage chemoattractant protein-1 (MCP-1), migration inhibitory factor (MIF), colony stimulating factor-1 (CSF-1), and interleukin-1 (IL-1) by ELISA. The CAFs or NFs were cocultured with EC cell lines to determine the proliferation, migration, and invasion by MTT assays and transwell chambers. Xenograft models were used to observe tumor growth. Matrix metalloproteinases (MMP)-2 and MMP-9 activity was evaluated by zymography. AMD3100 (a chemokine receptor 4 (CXCR4) antagonist) was used to block the SDF-1/CXCR4 axis. Neutralizing antibodies were used to detect PI3K/Akt and MAPK/Erk pathways by western blotting. SDF-1α and CXCR4 expressions were analyzed in xenotransplanted tumors and 348 cases by immunohistochemistry. RESULTS: CAFs promoted proliferation, migration, and invasion as well as in vivo tumorigenesis of admixed EC cells significantly more than NFs by secreting SDF-1α. These effects were significantly inhibited by AMD3100. CAFs promoted EC progression via the SDF-1α/CXCR4 axis to activate the PI3K/Akt and MAPK/Erk signalings in a paracrine-dependent manner or increase MMP-2 and MMP-9 secretion in an autocrine-dependent manner. SDF-1α and CXCR4 expression upregulation accompanied clinical EC development and progression. High SDF-1α expression levels were associated with deep myometrial invasion, lymph node metastasis, and poor prognosis in EC. CONCLUSIONS: Our data indicated that CAFs derived from EC tissues promoted EC progression via the SDF-1/CXCR4 axis in a paracrine- or autocrine-dependent manner. SDF-1α is a novel independent poor prognostic factor for EC patients' survival. Targeting the SDF-1/CXCR4 axis might provide a novel therapeutic strategy for EC treatment.