RESUMEN
BACKGROUND: Resistance can develop during treatment of advanced endometrial cancer (EC), leading to unsatisfactory results. Fanconi anemia complementation group D2 (Fancd2) has been shown to be closely related to drug resistance in cancer cells. Therefore, this study was designed to explore the correlation of Fancd2 with EC resistance and the mechanism of Fancd2. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression of Fancd2 in EC tissues and cells. EC cells (Ishikawa) and paclitaxel-resistant EC cells (Ishikawa/TAX) were transfected to knock down Fancd2. In addition, the ferroptosis inhibitor Ferrostatin-1 was adopted to treat Ishikawa/TAX cells. The sensitivity of cancer cells to chemotherapeutic agents was observed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and inhibitory concentration (IC)50 was calculated. Reactive oxygen species (ROS) levels were measured by flow cytometry, the activity of malondialdehyde (MDA) and the levels of glutathione (GSH) and Fe2+ in cells were detected by corresponding kits, and protein expression of solute farrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) was obtained through western blot. RESULTS: Compared with the normal tissues and endometrial epithelial cells, Fancd2 expression was significantly increased in EC tissues and Ishikawa cells, respectively. After knock-down of Fancd2, Ishikawa cells showed significantly increased sensitivity to chemotherapeutic agents. Besides, compared with Ishikawa cells, the levels of ROS, the activity of MDA, and the levels of GSH and Fe2+ were significantly decreased in Ishikawa/TAX cells, while the expression levels of SLC7A11 and GPX4 were significantly increased. Knock-down of Fancd2 significantly increased the ferroptosis levels in Ishikawa/TAX cells, but this effect could be reversed by Ferrostatin-1. CONCLUSION: Fancd2 increases drug resistance in EC cells by inhibiting the cellular ferroptosis pathway.
Asunto(s)
Ciclohexilaminas , Neoplasias Endometriales , Anemia de Fanconi , Ferroptosis , Fenilendiaminas , Femenino , Humanos , Especies Reactivas de Oxígeno/uso terapéutico , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genéticaRESUMEN
OBJECTIVE: Some studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early-stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early-stage CC. METHODS: Fifty-eight patients with CC (stage IB1-IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared. RESULTS: Patients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1-year disease-free survival rate and the 1-year overall survival rate were not significantly different between the two groups. CONCLUSION: There was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early-stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.
Asunto(s)
Histerectomía , Laparoscopía , Retención Urinaria , Neoplasias del Cuello Uterino , Femenino , Humanos , Histerectomía/efectos adversos , Laparoscopía/efectos adversos , Escisión del Ganglio Linfático/efectos adversos , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
PURPOSE: This study aimed to analyze left ventricular (LV) remodeling in patients with LV dilation using three-dimensional (3D) echocardiography, and to compare geometry and systolic function between patients with dilated cardiomyopathy (DCM) and with mitral regurgitation (MR) but similar LV dimension. METHODS: Cross-sectional study of 60 DCM and 60 MR patients with LV end diastolic diameter (LVEDD) > 35 mm/m2 , and of 60 healthy control volunteers. RESULTS: Despite a similar LVEDD, DCM patients showed a significantly higher 3D sphericity index (3D-SI) than MR patients, whereas 3D ejection fraction (3D-EF) was significantly lower (P < .01). There was a linear relationship between 3D-EF and 3D-SI in both DCM and MR patients (r = -0. 745 and r = -0. 642, respectively; both P < .001). Receiver operating characteristic (ROC) curves showed that 3D-SI had could better discriminate between DCM and MR (sensitivity 90%; specificity 73%; AUC 0.852, P < .01) than other variables. The area under the ROC curve of 3D-SI was significantly larger than that of 3D-EF for detecting heart failure in both patients with DCM and MR. CONCLUSIONS: LV geometry appears to be more spherical and associated with worse systolic function in DCM than in MR patients, in spite of similar LV dimensions. Systolic function correlated significantly with 3D-SI, which provided a better description of LV remodeling and could be a stronger indicator of heart failure in patients with LV dilation.
Asunto(s)
Cardiomiopatía Dilatada/diagnóstico por imagen , Ecocardiografía Tridimensional , Ventrículos Cardíacos/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Remodelación Ventricular , Adulto , Cardiomiopatía Dilatada/fisiopatología , Estudios de Casos y Controles , Estudios Transversales , Femenino , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/fisiopatología , Sensibilidad y Especificidad , Disfunción Ventricular Izquierda/etiologíaRESUMEN
Luteolin (Lu) exhibits a wide spectrum of anti-tumor activities, the present study was to observe whether Lu can sensitize breast cancer cells to doxorubicin (Dox) and to explain the basis underlying this phenomenon. In vitro, Lu at dose less than 100 microM had only slight effect on cells growth and cytotoxicity of Dox in 4T1 and MCF-7 cells under normoxia, but it could reverse tumor resistance to Dox and promote death of tumor cells under hypoxia. In vivo, Lu alone had also no effect on tumor growth delay, however, it could offer superior efficacy and lesser toxicity of Dox in 4T1 and MCF-7 bearing mice. Further study showed that Lu was able to suppress glycolytic flux but did not affect glucose uptake, the P-glycoprotein, anti-oxidative enzymes under hypoxia in vitro, and had not also effect on the intratumor Dox level in vivo. In addition, the activity of SOD and CAT was increased in serum and was decreased in tumor by Lu in vivo. These results suggest that luteolin as a glycolytic inhibitor might be a new adjuvant agent for chemotherapy.
Asunto(s)
Adyuvantes Farmacéuticos/farmacología , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Glucólisis/efectos de los fármacos , Luteolina/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Animales , Catalasa/sangre , Hipoxia de la Célula , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Doxorrubicina/toxicidad , Femenino , Glucosa/metabolismo , Humanos , Malondialdehído/sangre , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Superóxido Dismutasa/sangre , Superóxido Dismutasa-1RESUMEN
OBJECTIVE: To observe inducing differention effect on cells of serum from mice treated with Yang He decoction (SMY). METHODS: The viability of B16 cells was tested by lactate dehydrogenase (LDH) release assay and sulforhordamine B (SRB) assay. The differentiation of 3T3-L1 preadipocyte, HL-60, K562 and B16 cells were assessed by microscopy and Oil red O staining, NBT reduction and phagocytosis, haemoglobin (Hb) content and melanin content, respectively. RESULTS: SMY could obviously inhibit growth of B16 cells without cytotoxicity, and promote Oil red O staining in 3T3-L1 preadipocyte, enhance the NBT reduction ability and the phagocytosis of horse radish peroxidase in HL-60 cells, increase Hb content in K562 cells, and decrease melanin content in B16 cells. CONCLUSION: SMY is able to induce functional differentiation and maturation of 3T3-L1 preadipocyte and tumor cells, which implies the major mechanism of Yang He decoction in antitumor.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Diferenciación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Plantas Medicinales/química , Células 3T3-L1 , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Medios de Cultivo/farmacología , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Células HL-60 , Humanos , Células K562 , Masculino , Ratones , Fagocitosis/efectos de los fármacos , SueroRESUMEN
OBJECTIVE: To evaluate the therapy action of Sal-Ammoniac extract on Lewis lung cancer and its toxicity to immunity. METHODS: The proliferation and cell cycle of Lewis lung cancer cells were determined by MTT assay and flow cytometry respectively. The antitumor effect of Sal-Ammoniac extract was observed by tumor injected subcutaneously in mice and its toxicity to immunity was examined by clearance rate of charcoal particles and delayed type hypersensitivity. RESULTS: Sal-Ammoniac extract could inhibit the proliferation of Lewis lung cancer cells with S cell cycle arrest in a dose-dependent manner in vitro. Sal-Ammoniac extract solution injected in tumor for eight days had 46.7% inhibition on Lewis lung cancer, if taken orally had only 15.7% inhibition on Lewis lung cancer in mice. Sal-Ammoniac extract solution injected subcutaneously or taken orally had no effect on the clearance rate of charcoal particles and delayed type hypersensitivity in mice. CONCLUSION: The antitumor action of Sal-Ammoniac extract has relation to its recipe and has no influence on immunity.
Asunto(s)
Cloruro de Amonio/farmacología , Antineoplásicos/farmacología , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Materia Medica/farmacología , Cloruro de Amonio/administración & dosificación , Animales , Antineoplásicos/administración & dosificación , Carcinoma Pulmonar de Lewis/patología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Femenino , Citometría de Flujo , Materia Medica/administración & dosificación , Ratones , Ratones Endogámicos C57BLRESUMEN
Bcl-2 is best known for its anti-apoptotic function in a wide variety of cell types. The objective of this study was to investigate the effects of bcl-2 on the types of cell demise in the HeLa/bcl-2 cells induced by H2O2. The HeLa cell expressed stably bcl-2 was established and defined as the HeLa/bcl-2 cell strain, while the cell transfected with the empty expression vector was defined as the HeLa/vector cell strain. MTT assay revealed that the HeLa/bcl-2 cells showed a shorter life span. BrdU incorporation assay indicated that the bcl-2 exerted anti-demise effect on the HeLa/bcl-2 cells at the low concentration of H2O2. However, at the high concentration of H2O2, the death of the HeLa/bcl-2 cells was more than that of the HeLa/vector cells. The flow cytometry demonstrated that H2O2 mainly induced apoptosis in the HeLa/vector cells and elicited necrosis in the HeLa/bcl-2 cells. The addition of celecoxib to the cells treated by H2O2 could increase apoptosis in the HeLa/vector cells and convert necrosis into apoptosis in the HeLa/bcl-2 cells. The higher levels of cellular free radical and GSH were found in the HeLa/bcl-2 cells, but not in the HeLa/vector cells. With 200 microM H2O2 challenge for 48 h, the level of the cellular free radical was increased in the both strains, while the level of the GSH was decreased in the both strains. Celecoxib could reverse the difference between the both strains led by H2O2. Western blotting showed that the expression of COX-2 was always higher in the HeLa/bcl-2 cells than in the HeLa/vector cells under the both of treated and untreated with H2O2, while the level of COX-1 was relative stable in the both strains. These results suggested that the crosstalk between the bcl-2 and the COX-2 pathways could exist, the bcl-2 might up-regulate COX-2 to modify sensitivity to the types of demise in the HeLa/bcl-2 cell.
Asunto(s)
Apoptosis/efectos de los fármacos , Ciclooxigenasa 2/biosíntesis , Peróxido de Hidrógeno/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/fisiología , Ciclooxigenasa 2/análisis , Citocromos c/metabolismo , Glutatión/análisis , Células HeLa , Humanos , Necrosis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Regulación hacia ArribaRESUMEN
Thalidomide is an antiangiogenic drug and is clinically useful in a number of cancers. However, the molecular mechanism by which thalidomide exerts its antitumor effects is poorly understood. This study was designed to clarify the relationship between antiangiogenesis and antitumor effects of thalidomide and to explore the molecular mechanism for its antitumor activity. We evaluated the effects of thalidomide on the growth of human tumor cells expressing (MCF-7 and HL-60) or not expressing (HeLa and K562) COX-2 in vitro. We also studied the effects of thalidomide on COX-1, COX-2 or bcl-2 expression, TNFalpha, VEGF, GSH and cytochrome c in these cells. Thalidomide could inhibit tumor growth in a concentration-dependent manner in MCF-7 and HL-60; its IC50s for them were 18.36+/-2.34 and 22.14+/-2.15 microM, respectively, while this effect was not observed in HeLa and K562. Thalidomide reduced COX-2 expression accompanied by a decrease of bcl-2 protein, TNFalpha, VEGF, GSH and an increased cytochrome c, but had no effect on that of COX-1, in MCF-7 and HL-60. Moreover, cells not expressing COX-2 were insensitive to the growth-inhibitory and effects on cytokines of thalidomide. In our mouse xenograft model of OVCAR-3 and HCT-8, we found that thalidomide could decrease intratumoral microvessel density in both tumors; it exerted antitumor effects only on OVCAR-3 expressing COX-2 but did not on HCT-8 not expressing COX-2. Effect of thalidomide on COX-1 and COX-2 in vivo was consistent with that of in vitro. These results demonstrated that thalidomide might inhibit growth of tumors through COX-2 degradation independent of antiangiogenesis.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Talidomida/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Western Blotting , Línea Celular Tumoral , Citocromos c/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Glutatión/metabolismo , Células HL-60 , Células HeLa , Humanos , Células K562 , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neovascularización Patológica/enzimología , Neovascularización Patológica/prevención & control , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Talidomida/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
OBJECTIVE: To study the therapeutic effect of thalidomide (Tha) on murine hepatocellular carcinoma. METHODS: In murine transplanted hepatoma model, thalidomide was administered intragastrically alone (200 mg/kg daily for 10 days) or in combination with doxorubicin. The antitumor activity of Tha was observed in solid and ascitic tumor models. RESULTS: Tha induced significant growth inhibition of solid hepatoma without obvious toxicity on peripheral blood cells and lymphocyte proliferation. Although Tha alone had no effect on the survival of mice with ascitic tumor, it showed a synergistic antitumor activity in combination with doxorubicin (Dox) in both solid and ascitic tumor models. Moreover, Tha reduced Dox-induced cytopenia and immunosuppression. Histological analysis of Tha-treated tumors revealed remarkably enhanced tumor necrosis and lymphocyte infiltration on the edge of tumor tissues. CONCLUSION: Tha has definite therapeutic effect on murine hepatoma, and the combination with Dox shows an enhanced therapeutic potential.