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BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.
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Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Femenino , Humanos , Anciano , Adulto , Virus del Papiloma Humano , Estudios de Cohortes , Estudios Prospectivos , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Infecciones por Papillomavirus/tratamiento farmacológico , Papillomaviridae , GenotipoRESUMEN
BACKGROUND: The aim is to identify the factors influencing blood pressure variability in postmenopausal women based on the China Health and Nutrition Survey (CHNS). MATERIAL AND METHODS: The data on postmenopausal women between 1993 and 2015 were extracted from the CHNS. Group-based trajectory modeling was used to analyze the development track of blood pressure changes, based on which the subjects were separately divided into two groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP). Univariate and multivariate analyzes were performed to analyze the factors influencing SBP and DBP. RESULTS: A total of 346 women were eligible for the study. Group-based trajectory modeling showed two different trajectories of blood pressure, including the low-level, slowly developed type and the high-level, rapidly developed, stable type of SBP, as well as the low-level, slowly developed type and the high-level, slowly developed type of DBP. In multivariate analysis, age (odds ratio [OR]: 1.118, 95% confidence interval [CI]: 1.082-1.156), body mass index (BMI) (OR: 2.239, 95%CI: 1.010-4.964), antihypertensive agents (OR: 7.293, 95%CI: 2.191-24.275), hip circumference (OR: 1.069, 95%CI: 1.014-1.128) and marital status (OR: 3.103, 95%CI: 1.028-9.361) were found to be the significant factors influencing SBP; age (OR: 1.067, 95%CI: 1.039-1.096), alcohol consumption (OR: 2.741, 95%CI: 1.169-6.429), antihypertensive agents (OR: 4.577, 95%CI: 1.553-13.492), hip circumference (OR: 1.093, 95%CI: 1.049-1.138), and marital status (OR: 3.615, 95%CI: 1.228-10.644) were the predominant factors influencing DBP. CONCLUSIONS: In postmenopausal women, age, BMI, antihypertensive agents, hip circumference, and marital status are associated with SBP changes, while age, alcohol consumption, antihypertensive agents, hip circumference, and marital status with DBP variability. MESH KEYWORDS: postmenopausal women, blood pressure, development track, influencing factors, CHNS.
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Antihipertensivos , Hipertensión , Humanos , Femenino , Presión Sanguínea/fisiología , Posmenopausia , Índice de Masa Corporal , Encuestas Nutricionales , China/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Factores de RiesgoRESUMEN
Soft fibroma is a common benign skin tumour. The size varies from 1 to 10 mm, and giant soft fibromas were rare. Mostly, the appearances of soft fibromas were pedicled, filiform and papular. We reported a female adolescent with a giant penis-like soft fibroma in her vulva, meanwhile with an external genital malformation. We recalled our treatment process, including diagnosis and surgery, and aimed to broaden the understanding of soft fibroma through our case report.
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Fibroma , Neoplasias Cutáneas , Humanos , Masculino , Adolescente , Femenino , Fibroma/diagnóstico por imagen , Fibroma/cirugía , Neoplasias Cutáneas/diagnóstico , Diagnóstico Diferencial , Vulva/cirugía , Vulva/patologíaRESUMEN
High-risk human papillomavirus (hrHPV) persistent infection is the major cause of cervical cancer. Clinical intervention of hrHPV-associated high-grade squamous intraepithelial lesion (HSIL) is critical to prevent cervical cancer, and current treatment is surgery (an invasive therapy). However, some patients refuse to do so for an afraid of potential adverse effects on future fertility or other concerns which creates a critical need for development of non-invasive therapeutic strategies. Here, we report for the first time the cases of non-invasive intervention with REBACIN®, a proprietary antiviral biologics, in clinical treatment of HSIL. From 12,958 visiting patients assessed for eligibility, 18 HSIL-patients with cervical intraepithelial neoplasia-grade 2, positive of both diffused overexpression of p16 and high-risk HPV were enrolled in this non-invasive clinical intervention mainly due to concerns of future fertility. REBACIN® was administered intravaginally every other day for 3 months (one-course) except during menstrual period, and were followed up for 6-36 months for the examination of high-risk HPV DNA, cervical cytology, and histopathology. After one to three course treatments, most cases (16/18) displayed both the regression from HSIL (CIN2) to normal cervical cytology and clearance of high-risk HPV infection. Further studies demonstrated REBACIN® significantly suppressed HPV16 E7 oncoprotein expression in a human cervical cancer cell line, which is consistent with previous finding that REBACIN® inhibits the growth of tumors induced by expression of E6/E7 oncogenes of either HPV16 or HPV18. This report indicates REBACIN® as a novel effective non-invasive clinical intervention for HSIL-patients as well for high-risk HPV persistent infection, providing a new clinical option for the non-invasive treatment of hrHPV-associated high-grade squamous intraepithelial lesion, which is worthy of further research on clinical validation and application.
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Inorganic pyrophosphatases (PPases) catalyze the hydrolysis of pyrophosphate to phosphates. PPases play essential roles in growth and development, and are found in all kingdoms of life. Human possess two PPases, PPA1 and PPA2. PPA1 is present in all tissues, acting largely as a housekeeping enzyme. Besides pyrophosphate hydrolysis, PPA1 can also directly dephosphorylate phosphorylated c-Jun N-terminal kinases 1 (JNK1). Upregulated expression of PPA1 has been linked to many human malignant tumors. PPA1 knockdown induces apoptosis and decreases proliferation. PPA1 is emerging as a potential prognostic biomarker and target for anti-cancer drug development. In spite of the biological and physiopathological importance of PPA1, there is no detailed study on the structure and catalytic mechanisms of mammalian origin PPases. Here we report the crystal structure of human PPA1 at a resolution of 2.4 Å. We also carried out modeling studies of PPA1 in complex with JNK1 derived phosphor-peptides. The monomeric protein fold of PPA1 is similar to those found in other family I PPases. PPA1 forms a dimeric structure that should be conserved in animal and fungal PPases. Analysis of the PPA1 structure and comparison with available structures of PPases from lower organisms suggest that PPA1 has a largely pre-organized and relatively rigid active site for pyrophosphate hydrolysis. Results from the modeling study indicate the active site of PPA1 has the potential to accommodate double-phosphorylated peptides from JNK1. In short, results from the study provides new insights into the mechanisms of human PPA1 and basis for structure-based anti-cancer drug developments using PPA1 as the target.
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Difosfatos/química , Pirofosfatasa Inorgánica/química , Proteínas Mitocondriales/química , Proteína Quinasa 8 Activada por Mitógenos/química , Fosfatos/química , Secuencia de Aminoácidos , Dominio Catalítico , Clonación Molecular , Cristalografía por Rayos X , Difosfatos/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Humanos , Pirofosfatasa Inorgánica/genética , Pirofosfatasa Inorgánica/metabolismo , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteína Quinasa 8 Activada por Mitógenos/genética , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Modelos Moleculares , Fosfatos/metabolismo , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Pliegue de Proteína , Dominios y Motivos de Interacción de Proteínas , Multimerización de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Especificidad por SustratoRESUMEN
Endocrine therapy (mainly anti-estrogen therapy) is the mainstay of treatment for estrogen receptor (ER) positive breast cancer (BCa). However, approximately one-third of BCa patients who receive endocrine therapy may develop resistance. The detailed mechanism is still unclear. MCF7 and T-47D cells were treated with ERα antagonist tamoxifen for 2 months until they became tamoxifen-resistant. qPCR was used to detect the stem markers like CD44, OCT4 and SOX2. Flow cytometry and sphere formation were performed to test the stemness. Cell growth and invasiveness were measured by MTS assay, xenograft mouse model, and invasion assay. We found that tamoxifen resistant BCa cells acquired certain malignant phenotypes, such as higher expression of KLF4, stemness and enhanced invasiveness. Furthermore, miR-484 was found to act as a tumor suppressor and directly downregulated KLF4. KLF4-induced cancer stem cell (CSCs) contributes to anti-ER therapy resistant and is a potential target in endocrine therapy-resistant cancers.
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Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Factores de Transcripción de Tipo Kruppel/genética , MicroARNs/metabolismo , Animales , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Receptor alfa de Estrógeno/análisis , Receptor alfa de Estrógeno/antagonistas & inhibidores , Receptor alfa de Estrógeno/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/metabolismo , Células MCF-7 , Ratones , Invasividad Neoplásica/genética , Células Madre Neoplásicas/metabolismo , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
AIM: Recent years have witnessed an elevated incidence of cesarean scar pregnancy (CSP). However, the clinical complications and consequences of uterine artery embolization (UAE) and curettage treatment for CSP patients are not clear. We aimed to assess menstrual recovery and other clinically pertinent factors after UAE and curettage treatment in CSP patients. METHODS: A total of 169 CSP patients who underwent UAE combined with curettage between August 2013 and August 2017 were enrolled in this study. The menstruation recovery was recorded, and the factors that potentially affected menstrual blood volume (MBV) were analyzed. RESULTS: Among the 169 CSP cases, 36 had asymptomatics (21.3%), 133 vaginal hemorrhage (78.7%) and 19 lower abdominal pain (11.2%). The success rate of treatment was 96.4% with six patients undergoing further treatment. The follow-up assessment was performed in 139 of 169 patients. About 83 of 139 (59.7%) patients had reduced MBV, and 2 patients (1.4%) had amenorrhea. There was a significant difference in numbers of abortions between the decreased and normal MBV group (P = 0.0276). Importantly, 16 of 42 cases who were planning on having babies became pregnant, with 8 from the decreased (8/27) and normal MBV (8/15) group each. CONCLUSION: UAE combined with curettage treatment in CSP patients demonstrates a favorable success rate, which can also reduce MBV and proceeding pregnancy rate.
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Embolización de la Arteria Uterina , Cesárea/efectos adversos , Cicatriz , Legrado , Femenino , Humanos , Metotrexato , Embarazo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
AIM: An IUD perforating the uterus and bladder and creating a nidus for stone formation is a rare complication. We aim to demonstrate with a video a novel surgical technique that involves transcervically extracting a perforating IUD with a transurethral nephroscope after removal of the bladder stone on the IUD. METHODS: A 57-year-old woman was referred to our department 4 months ago following a 2-year history of suprapubic pain at the end of urination. Ultrasound and X-ray examination confirmed an IUD perforating the uterus and the bladder. The patient underwent transurethral holmium laser lithotripsy and transcervical removal of the IUD with the aid of a transurethral nephroscope. RESULTS: The stone on the perforating ectopic IUD was successfully removed and the IUD was extracted without complications. CONCLUSION: This video demonstrates a rare case of an IUD that perforated both the bladder and the uterine walls and created a nidus for stone formation in the bladder. The surgical technique involved in removing the stone and extracting the IUD is a new approach to treating this problem. It is suspected that this specific surgical intervention may also help to minimize the formation of a larger vesico-uterine fistula by decreasing the extent of trauma potentially created when extracting the IUD. However, this supposition merits further study.
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Remoción de Dispositivos/métodos , Migración de Dispositivo Intrauterino/efectos adversos , Litotricia/métodos , Uretra/cirugía , Perforación Uterina/cirugía , Dolor Abdominal/etiología , Dolor Abdominal/cirugía , Femenino , Humanos , Dispositivos Intrauterinos/efectos adversos , Persona de Mediana Edad , Rotura , Vejiga Urinaria/lesiones , Perforación Uterina/etiología , Útero/lesionesRESUMEN
Endoplasmic reticulum (ER) is an essential site of cellular homeostasis regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from apoptosis. The present study examined the effects and mechanism of ERS on cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with Saquinavir were subjected to western blot and reverse transcription-quantitative polymerase chain reaction analysis to determine protein and messenger RNA (mRNA) expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1. MTT assay was used to analyze the influence of Saquinavir on DDP resistance in SKOV3 cells. Saquinavir induced glucose-regulated protein 78 expression, which is a marker of ERS. Following treatment with various doses of Saquinavir, the sensitivity of ovarian cancer cells to DDP decreased significantly. Protein and mRNA expression levels of mTOR and Beclin 1 in SKOV3 cells were increased when the cells were exposed to Saquinavir or DDP for 24 h. Moreover, mTOR and Beclin 1 expression levels were highest in the Saquinavir + DDP group (0.684±0.072 and 0.6467±0.0468, respectively). SKOV3 tumor cells were also exposed to the autophagy inhibitor, 3-methyladenine (3-MA), and different concentrations of Saquinavir. Analysis of half maximal inhibitory concentration (IC50) values of DDP after this treatment demonstrated that IC50 values were significantly decreased compared with Saquinavir alone (P<0.001), suggesting that the sensitivity to DDP was improved in ovarian cancer cells after 3-MA exposure. These findings demonstrated that Saquinavir is able to induce ERS in SKOV3 cells effectively, and ER-induced stress may decrease the sensitivity of DDP in SKOV3 cells. Furthermore, ERS may regulate cell autophagy through the mTOR and Beclin 1 pathways, leading to a reduction in the sensitivity of DDP in SKOV3 cells. ERS in tumor cells and autophagy may be a potential target to improve the therapeutic effect of chemotherapy and reduce drug resistance in tumors.
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Tamoxifen has been widely used to treat breast cancer as an endocrine therapy. However, tamoxifen is known to enhance the risk of developing endometrial cancer. We want to examine the effect of tamoxifen on endometrial cancer. In our retrospective study, we found that high grade, high stage, and lymph node metastasis were more common in tamoxifen users. In vitro 4-hydroxytamoxifen (OHT) induced cell proliferation and cell cycle promotion in type I and type II endometrial cancer cell lines, and this proliferation was blocked by GPER silencing. Treatment with OHT increased EGFR and ERK phosphorylation and the mRNA and protein levels of cyclin D1 and GPER. Taken together, our data demonstrate that endometrial cancer patients with tamoxifen treatment exhibit more aggressive histological subtypes and worse prognosis. OHT is a proliferation-inducing agent for endometrial cancer cells, and the GPER/EFGR/ERK/cyclin D1 pathway is involved in this process.
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Ciclina D1/metabolismo , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Tamoxifeno/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Fosforilación/efectos de los fármacos , Estudios RetrospectivosRESUMEN
OBJECTIVE: Determine the serum adiponectin levels in endometrial carcinoma (EC) cases and controls and explore the correlation between them. We assessed the functions of AdipoR1 and AdipoR2 in endometrial cancer cells to determine whether the AMPK/ERK and Akt pathways mediate the effects of adiponectin-induced apoptosis and anti-proliferation. MATERIAL AND METHODS: The serum adiponectin levels were measured via enzyme-linked immunosorbent assay (ELISA). The proliferation and apoptosis rates were determined with MTT and annexin V/PI assays. To evaluate the activation of AMPK, ERK, and Akt and the expression of Bcl-2 and Cyclin D1, western blot analysis was performed in Ishikawa 3-H-12 cells. We down-regulated AdipoRs by si-RNA to assess their functions. RESULTS: The serum adiponectin levels were significantly decreased in patients with EC compared to controls. The adiponectin-induced apoptosis and anti-proliferation effects in EC cells were blocked by Compound C. Ishikawa 3-H-12 cells exhibited time- and dose-dependent increases in the p-AMPK levels after treatment with adiponectin. Adiponectin treatment reduced the levels of ERK and Akt phosphorylations and cyclin D1 and Bcl-2 mRNA and protein expression. Compound C blocked the effects on ERK, Akt, cyclin D1, and Bcl-2. AdipoR1 and AdipoR2 were involved in adiponectin-induced growth inhibition and ERK activation inhibition. We speculated that AdipoR1 has a greater role than adipoR2 in apoptosis and Akt activation inhibition after adiponectin treatment. CONCLUSION: Adiponectin was an apoptotic and anti-proliferation agent for EC cells, and these effects were dependent on the AMPK/ERK and Akt pathways. AdipoR1 and AdipoR2 may play different roles in this process.
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Proteínas Quinasas Activadas por AMP/metabolismo , Adiponectina/sangre , Neoplasias Endometriales/sangre , Neoplasias Endometriales/patología , Receptores de Adiponectina/metabolismo , Adiponectina/farmacología , Anciano , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Estudios de Casos y Controles , Línea Celular Tumoral , Neoplasias Endometriales/enzimología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Persona de Mediana Edad , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Recombinantes/farmacologíaRESUMEN
OBJECTIVE: To explore the effect and mechanism of glucose regulated protein 78 (GRP78) on autophagy and apoptosis in ovarian carcinoma, and to investigate the influence on the growth and sensitivity to cisplatin on the ovarian cancer cells. METHODS: The human ovarian cancer cell line SKOV3 were treated by the GRP78 regulator BAPTA-AM and A23187, which were used to decrease or increase the expression levels of GRP78, respectively. The experiment were divided into three groups. Cells in the group of BAPTA-AM were treated by BAPTA-AM at the final concerntration of 40 µmol/L for 1 hour. Cells in the group of A23187 were treated by A23187 at the final concerntration of 4 µmol/L for 24 hours. While, cells in the control group were treated by culture medium without any GRP78 regulator for 24 hours. The expressions of GRP78, beclin1, Bcl-2 and CHOP mRNA and protein were detected by reverse transcription (RT)-PCR and western blot. The autophagy levels was observed by green fluorescent protein-microtubule-associated protein 1 light chain 3-II (GFP-LC3-II) fluorescence staining. The flow cytometry was used to analyse the apoptosis rates of cells. The effect on cell growth and the sensitivity to cisplatin of SKOV3 were accessed by methyl thiazolyl tetrazolium (MTT). RESULTS: (1) The mRNA expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of BAPTA-AM were 0.583±0.025, 0.860±0.055, 0.714±0.032 and 0.811±0.004, respectively. The mRNA expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of A23187 were 0.840±0.044, 0.654±0.065, 0.908±0.047 and 0.620±0.062, respectively. The mRNA expressions of GRP78, beclin1, Bcl-2 and CHOP in the control group were 0.687±0.032, 0.772±0.029, 0.845±0.018, 0.712±0.077, respectively. While the protein expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of BAPTA-AM were 0.423±0.035, 0.952±0.022, 0.385±0.032, 0.681±0.095, respectively. The protein expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of A23187 were 0.743±0.032, 0.638±0.025, 0.596±0.029, 0.431±0.095, respectively. The protein expressions of GRP78, beclin1, Bcl-2 and CHOP in the control group were 0.617±0.031, 0.789±0.083, 0.492±0.036, 0.531±0.003, respectively. The mRNA and protein expressions of beclin and CHOP in the group of BAPTA-AM were both higher than those in the control group (P<0.05). While, the mRNA and protein expressions of beclin and CHOP in the group of A23187 were both lower than those in the control group (P< 0.05). (2) The autophagy fluorescence of SKOV3 in the group of BAPTA-AM, A23187 and the control group were 706±117, 473±128, 595±126, respectively, in which there were significant differences among three groups (P<0.05). (3) The apoptosis rate of SKOV3 in the group of BAPTA-AM was (27.4±2.2)%, which was higher than that in the control group [(19.6±1.4)%, P<0.05]. The apoptosis rate of SKOV3 in the group of A23187 was (12.2±1.9)%, which was lower than that in the control group (P<0.05). (4) The comparison of the sensitivity to cisplatin in 3 groups of SKOV3. The 50% inhibition concentration (IC50) of SKOV3 to cisplatin was (3.02±0.62) mg/L. After treated by BAPTA-AM + cisplatin, the IC50 was (2.00±0.17) mg/L and the sensitivity of SKOV3 to cisplatin was increased by 33.8%, and there was significant difference (P<0.05), compared with the control group. And after treated by A23187 + cisplatin, the IC50 was (4.91±2.52) mg/L and the sensitivity of SKOV3 to cisplatin was decreasd by 62.6%; and there was significant difference (P<0.05), compared with the control group. CONCLUSION: GRP78 could regulate autophagy and apoptosis of ovarian cancer cells by regulating the expressions of beclin1, Bcl-2 and CHOP, thereby affecting the sensitivity to cisplatin in ovarian carcinoma, which may be a new method for the treatment and improvement of the sensitivity to cisplatin in ovarian carcinoma.
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Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Proteínas de Choque Térmico/metabolismo , Neoplasias Ováricas/tratamiento farmacológico , Antineoplásicos/farmacología , Proteínas Reguladoras de la Apoptosis , Ciclo Celular , Línea Celular Tumoral , Ácido Egtácico/análogos & derivados , Chaperón BiP del Retículo Endoplásmico , Femenino , Glucosa , Proteínas de Choque Térmico/genética , Humanos , Proteínas Asociadas a Microtúbulos , Neoplasias Ováricas/metabolismo , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Perforation by intrauterine devices (IUDs) can involve. neighboring organs such as the bladder. CASE: A 29-year-old woman with 2 previous cesarean section deliveries was diagnosed in the early stage of pregnancy with an IUD that had partially perforated the bladder. The exact location of the migrated IUD was determined with pelvic ultrasonography and endoscopic techniques, and the IUD was successfully retrieved with a hysteroscope. CONCLUSION: The use of imaging studies and endoscopic techniques such as ultrasonic examination, hysteroscopy, and cystoscopy are essential for identifying the location of an IUD that has partially perforated the bladder. Depending on the application of the correct treatment method, good results can be achieved following partial perforation of the bladder by an IUD.
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Migración de Dispositivo Intrauterino/efectos adversos , Dispositivos Intrauterinos/efectos adversos , Vejiga Urinaria/lesiones , Adulto , Cistoscopía , Femenino , Humanos , Histeroscopía , EmbarazoRESUMEN
OBJECTIVE: The study intended to investigate the effect and mechanism of endoplasmic reticulum stress on cisplatin resistance in ovarian carcinoma. METHODS: RT-PCR and Western blot were used to test the expression of mTOR and Beclin1 mRNA and protein in ovarian cancer SKOV3 cells after saquinavir induction. MTT assay was used to analyze the influence of saquinavir on cisplatin sensitivity in SKOV3 cells. RESULTS: The IC50 of SKOV3 cells was (5.490 ± 1.148) µg/ml. After induced by Saquinavair 10 µmol/L and 20 µmol/L, the IC50 of SKOV3 cells was increased to (11.199 ± 0.984) µg/ml and (14.906 ± 2.015) µg/ml, respectively. It suggested that the sensitivity of ovarian cancer cells to cisplatin was decreased significantly (P = 0.001). The expression of mTOR and Beclin1 mRNA and protein was significantly different among the five groups: the (Saquinavair+DDP) group of, Saquinavair group, LY294002 group, DDP group and control group (P < 0.001) . The expressions of mTOR and Beclin1 mRNA were highest in the (Saquinavair+DDP) group, 0.684 ± 0.072 and 0.647 ± 0.047, respectively; Secondly, the Saquinavair group, 0.577 ± 0.016 and 0.565 ± 0.037, respectively. The expressions of mTOR and Beclin1 proteins were also highest in the (Saquinavair+DDP) group, 0.624 ± 0.058 and 0.924 ± 0.033, respectively, followed by the Saquinavair group, 0.544 ± 0.019 and 0.712 ± 0.024. 3-MA inhibited the autophagy and restored cisplatin sensitivity in the SKOV3 cells after Saquinavir induced ER stress (P < 0.001). CONCLUSIONS: Saquinavir can effectively induce endoplasmic reticulum stress in SKOV3 cells. Endoplasmic reticulum stress can decrease the sensitivity to cisplatin in SKOV3 cells. The mechanism of the decrease of sensitivity to cisplatin in SKOV3 cells may be that ERS regulates cell autophagy through the mTOR and Beclin1 pathways. ERS of tumor cells and autophagy may become a new target to improve the therapeutic effect of chemotherapy and to reverse the drug resistance in tumor treatment.
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Cisplatino/farmacología , Cistadenocarcinoma Seroso/patología , Resistencia a Antineoplásicos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Neoplasias Ováricas/patología , Saquinavir/farmacología , Antineoplásicos/farmacología , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/efectos de los fármacos , Beclina-1 , Línea Celular Tumoral , Cistadenocarcinoma Seroso/metabolismo , Femenino , Inhibidores de la Proteasa del VIH/farmacología , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Neoplasias Ováricas/metabolismo , ARN Mensajero , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: The effect of histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors (DNMTIs) on proliferation of endometrial cancer (EC) cells in vitro and in vivo was investigated. METHODS: Changes in methylation of the CDH1 promoter in HDACI- and DNMTI-treated HEC-1-B and RL-952 EC cells were detected. Nude mice with xenografted implants of human EC HEC-1-B cells were treated with valproic acid (VPA) and decitabine (DAC) and evaluated for tumor growth, CDH1 and Bcl-2 mRNA levels. RESULTS: DAC, VPA and suberoylanilide hydroxamic acid (SAHA) inhibited proliferation, induced cell cycle arrest and enhanced the apoptotic index in both cell lines, DAC, VPA and SAHA upregulated E-cadherin mRNA and protein levels and downregulated Bcl-2 mRNA levels in vitro. DAC and VPA inhibited tumor growth, upregulated CDH1 mRNA and downregulated Bcl-2 mRNA levels in vivo. CONCLUSIONS: A combination of HDACIs and DNMTIs suppresses the growth of EC, which is likely mediated by upregulation of E-cadherin and downregulation of Bcl-2.
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Cadherinas/metabolismo , Carcinoma/tratamiento farmacológico , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , Neoplasias Endometriales/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Azacitidina/análogos & derivados , Azacitidina/farmacología , Azacitidina/uso terapéutico , Cadherinas/genética , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , Decitabina , Inhibidores Enzimáticos/uso terapéutico , Femenino , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Ratones , Ratones Desnudos , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Trasplante Heterólogo , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoRESUMEN
The primary aim of this study is to evaluate the clinical significance of E-cadherin protein expression and the methylation status in CDH1 promoter in endometrial cancer. The expression of E-cadherin and methylation in its promoter region was analyzed, retrospectively, in 152 clinical tissue samples from patients with endometrial lesions. We found that the hypermethylation of CDH1 promoter, which caused low expression of E-cadherin in endometrial cancer, was associated with not only clinicopathological progress of endometrial cancer but also with the overall 5-year clinical survival rate. The findings provide the potential therapeutic and prognostic target molecule for patients with endomethrial cancer.
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Cadherinas/análisis , Cadherinas/genética , Carcinoma/química , Carcinoma/genética , Metilación de ADN , Neoplasias Endometriales/química , Neoplasias Endometriales/genética , Regiones Promotoras Genéticas , Antígenos CD , Carcinoma/mortalidad , Carcinoma/patología , China , Regulación hacia Abajo , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: To study the relationship between nucleotide excision repair gene ERCC1 and resistance to cisplatin in ovarian cancer. METHODS: The expression of gene ERCC1 in 58 ovarian cancer tissues and 4 cell lines were examined and its relationship with resistance to cisplatin were analyzed, the changes of sensitivity to cisplatin were observed after interference of ERCC1 gene with small interfering RNA (siRNA) in ovarian cancer cell lines. RESULTS: In 58 ovarian cancer tissues, the positive rate of ERCC1 protein in chemoresistant cases (57.89%) was higher than that in chemo-sensitive cases (28.21%, P = 0.029). The mRNA levels of ERCC1 gene in ovarian cancer cell lines ES-2, SKOV3, COC1, COC1/DDP were related to cisplatin IC50 values (r = 0.932, P <0.05). The sensitivity of cell lines ES-2, SKOV3, COC1/DDP cells to cisplatin was increased by 53.88, 5.07, and 3.75 times, respectively, after RNA interfering ERCC1 gene. CONCLUSION: ERCC1 gene is associated with the resistance to cisplatin and the sensitivity to cisplatin can be enhanced by RNA interfering ERCC1 in ovarian cancer.
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Cisplatino/farmacología , Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos , Endonucleasas/metabolismo , Neoplasias Ováricas/metabolismo , ARN Interferente Pequeño/genética , Adulto , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Reparación del ADN , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Humanos , Concentración 50 Inhibidora , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Interferencia de ARN , ARN Mensajero/metabolismo , Transfección , Adulto JovenRESUMEN
OBJECTIVE: To study the changes of DNA repair genes and enhanced anti-tumor effect of cisplatin induced by mifepristone in human ovarian cancer drug resistance cells. METHODS: The alterations of cisplatin concentration producing 50% inhibition (IC50 ) in the COC1/DDP cell lines were examined by methyl thiazolyl tetrazolium (MTT) assay. RT-PCR and flow cytometry were used to analyze the changes of the mRNA of ERCC1, BRCA1, hMLH1 genes and cell cycle and apoptosis. Subcutaneous implantation of COC1/DDP was established in nude mice and the enhanced anti-tumor effect of cisplatin by mifepristone was observed in vivo. RESULTS: Cisplatin IC50 values of COC1/DDP cell were decreased from (3.71 +/- 0.38) microg/ml to (3.18 +/- 0.46), (1.95 +/- 0.14), (0.64 +/- 0.18) microg/ml respectively when treated with 2.5, 5.0, 10.0 micromol/L mifepristone. Mifepristone could down-regulate the mRNA levels of ERCC1, BRCA1, hMLH1 genes and enhance G0/G1 phase block effect of cisplatin, and 2.5, 5.0, 10.0 micromol/L mifepristone combined with cisplatin increased rate of cell apoptosis from 0.08% to 5.11%, 9.13% and 12.24% respectively. The percentage of inhibition of xenograft tumor volume in combined treatment group was 70.1%, which was significantly different (P < 0.05). CONCLUSION: By down-regulating ERCC1, BRCA1, hMLH1 genes, blocking G0/G1 phase, and increasing apoptosis rate, mifepristone could enhance anti-tumor effect of cisplatin.
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Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Reparación del ADN , Mifepristona/farmacología , Neoplasias Ováricas/patología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Antineoplásicos/farmacología , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Cisplatino/administración & dosificación , Daño del ADN , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Endonucleasas/genética , Endonucleasas/metabolismo , Femenino , Humanos , Ratones , Ratones Desnudos , Mifepristona/administración & dosificación , Homólogo 1 de la Proteína MutL , Trasplante de Neoplasias , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
OBJECTIVE: To study changes of cisplatin sensitivity by RNA interfering the excision repair cross-complementing (ERCC) 1 gene in ovarian cancer cell lines. METHODS: The small interference RNA (siRNA) targeting ERCC1 gene was designed and synthesized by transcription in vitro, and transfected to ovarian cancer cell line ES-2. The mRNA and protein of ERCC1 were evaluated by means of RT-PCR, western blot and immunocytochemistry. The changes of cisplatin sensitivity after interference were examined by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: In ES-2 cell, the mRNA and protein levels of ERCC1 were dramatically decreased 24, 48 and 72 hours after transfection. The sensitivity to cisplatin of ES-2 cell line was increased by 53.88 times after disturbing the ERCC1 gene. CONCLUSION: The sensitivity to cisplatin of ovarian cancer cell lines ES-2 could be enhanced by RNA interfering ERCC1 gene.