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1.
Cancer Invest ; 38(8-9): 493-501, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32845165

RESUMO

Primary pulmonary choriocarcinoma (PPC) is frequently fatal due to difficulties in diagnosis. Few cases of PPC are bilateral and involve exceptionally large nodules. Here, we report an unusual case of PPC involving disseminated bilateral nodules, which was misdiagnosed as tuberculosis, but successfully treated using chemotherapy. A review of 65 cases revealed six cases of bilateral disease, including the present one. Patients treated with surgery, chemotherapy, or a combination of both showed similar treatment outcomes; however, chemotherapy may be the preferred option. Despite its rarity, PPC should be included in the differential diagnosis for all lung nodules to enable early detection.


Assuntos
Coriocarcinoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Coriocarcinoma/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico
2.
Molecules ; 25(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093273

RESUMO

5,6,7,8,3,4'-Hexamethoxyflavone, also called nobiletin (NOB), widely found in the citrus peel, is one of the main byproducts in citrus processing. NOB is considered safe, but its safety for women during pregnancy is unknown. Therefore, the effect of NOB on apoptosis in human choriocarcinoma trophoblast cells (BeWo cells) was evaluated. Cells were divided into four groups and cultured with different concentrations of NOB (0, 10, 33, and 100 µM) for 12, 24, 36, and 48 h respectively. Cell viability was detected by CCK-8 assay, cell morphology was detected by a Cell Imaging Multi-Mode Reader, and cell cycle and apoptosis were detected by flow cytometry. Cleaved PARP level, the expressions of B cell lymphoma 2 (BCL2) family proteins, and p53 pathway proteins were detected by Western blot. The results showed that after 48 h of cell culture, the cell viability was decreased significantly, but apoptosis was significantly increased. Compared to the cells without NOB treatment, the cells treated with NOB at 10 or 33 µΜ showed no significant differences in the number of suspended cells or late apoptosis rate, except the increase of cell viability. Treatment of NOB at the concentration of 100 µM improved cell viability, attenuated apoptosis, decreased suspended cells, and did not alter the G1 phase arrest, compared with the non-NOB-treated group after 48 h of culturing. The 100 µΜ NOB treatment increased the levels of BCL2 and BCLXL, and decreased p53 accumulation in BeWo cells at 48 h, but had no effect on the expression of BAX, BAK, BAD, p21, and G1 phase arrest. These findings provide evidence that NOB (10, 33, and 100 µΜ) was safe for BeWo cells. NOB at the concentration of 100 µΜ could attenuate apoptosis in BeWo cells, which might be helpful to prevent pregnancy-related diseases caused by apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Coriocarcinoma , Flavonas/farmacologia , Trofoblastos , Neoplasias Uterinas , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Feminino , Humanos , Proteínas de Neoplasias/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
3.
Gynecol Oncol ; 157(1): 268-279, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31955862

RESUMO

OBJECTIVE: Although methotrexate (MTX) is commonly used for the treatment of choriocarcinoma, chemoresistance to MTX may occur in a considerable fraction of patients. Further understanding on the mechanisms of MTX resistance would help to develop more effective therapy for choriocarcinoma. METHODS: Quantitative proteomic approach involving TMT labeling and LC-MS/MS was used to identify MTX resistance-related proteomic profiles in choriocarcinoma cell models. Pathway and process enrichment analysis were conducted to identify MTX resistance-related biological processes/molecular pathways. CCK-8 viability assay, clonogenic survival assay, and BrdU incorporation analysis were used to examine the chemosensitivity to MTX in choriocarcinoma cells. RESULTS: In total, 5704 protein groups were identified, among which 4997 proteins were quantified. Bioinformatic analysis revealed that multiple biological processes/molecular pathways might be associated with MTX resistance in JEG3/JEG3/MTX cell systems. DPP4 and METTL7A were selected for further investigation. Increased expression of DPP4 or METTL7A was observed in MTX-resistant cancer cell lines and choriocarcinoma tissues. Knockdown of DPP4 or METTL7A significantly decreased cell viability, impaired clonogenesis, and increased apoptosis after MTX treatment in JEG3/MTX and JAR/MTX cells; while over-expression of DPP4 or METTL7A promoted cell viability and reduced apoptosis following exposure to MTX in JEG3, JAR and BEWO cells. Further, DPP4 and METTL7A differentially activated prosurvival signaling pathways including PI3K/AKT, ERK1/2 and STAT3, and attenuated the accumulation of reactive oxygen species (ROS) in choriocarcinoma cell lines. CONCLUSIONS: DPP4 and METTL7A might promote MTX resistance through activating pro-survival signaling pathways and attenuating the accumulation of ROS in choriocarcinoma cells. Targeting DPP4 and METTL7A might be useful to sensitize choriocarcinoma cells to MTX-based chemotherapy.


Assuntos
Coriocarcinoma/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Metotrexato/farmacologia , Metiltransferases/metabolismo , Neoplasias Uterinas/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Coriocarcinoma/enzimologia , Cromatografia Líquida , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Gravidez , Mapeamento de Interação de Proteínas , Proteômica/métodos , Transdução de Sinais , Espectrometria de Massas em Tandem , Neoplasias Uterinas/enzimologia
4.
BJOG ; 127(3): 389-395, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31794098

RESUMO

OBJECTIVE: Presence of lung metastases in low-risk gestational trophoblastic neoplasia (GTN) is generally considered not to influence prognosis. However, in a recent study in the Netherlands, GTN patients with lung metastases had a higher recurrence rate and more disease-specific deaths compared with patients without metastases. The aim of the present study was to validate these findings in a different country. DESIGN: Historical cohort study. SETTING: Charing Cross Hospital, United Kingdom. POPULATION: A total of 1040 low-risk GTN patients treated with methotrexate (MTX) between 2002 and 2016 were identified: 65 with lung metastases (group 1) and 975 without metastases (group 2). METHODS: Baseline characteristics, MTX resistance, survival and recurrence rates were recorded and compared between both groups. MAIN OUTCOME MEASURES: MTX resistance, recurrence rate and survival. RESULTS: The occurrence of MTX resistance and median number of MTX courses to achieve remission was significantly higher in patients with lung metastases than patients without metastases (60% versus 38.9%, P = 0.001; and nine versus six courses, P < 0.001). All choriocarcinoma patients (n = 4) with lung metastases developed MTX resistance. The recurrence rate was also higher in group I (9.2% versus 2.7%; P = 0.012). Disease-specific survival was 100% in both groups. CONCLUSIONS: The presence of lung metastases at the start of MTX therapy is associated with increased incidence of MTX resistance and recurrence in low-risk GTN without affecting overall survival, which remains 100%. However, individuals with low-risk choriocarcinoma with lung metastases are likely to become resistant to MTX and primary multi-agent chemotherapy should be considered. TWEETABLE ABSTRACT: The presence of lung metastases appears to increase the risk of recurrence in low-risk GTN, but does not affect overall cure rates and survival.


Assuntos
Coriocarcinoma , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Metotrexato , Adulto , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Estudos de Coortes , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Países Baixos/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Recidiva , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Reino Unido/epidemiologia
5.
Int J Clin Oncol ; 25(1): 203-209, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520175

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide, and actinomycin D (MEA) for patients who were diagnosed with choriocarcinoma and high-risk gestational trophoblastic neoplasia (GTN). METHODS: Between January 1999 and December 2015, 29 patients were treated with 4-day MEA after being diagnosed with choriocarcinoma or high-risk GTN. Complete remission to 4-day MEA and adverse effects were retrospectively evaluated. RESULTS: The complete remission rates were 79.3% (23/29) and 87.5% (21/24) in all patients and in those who received 4-day MEA as first-line therapy, respectively. Of six patients who developed drug resistance to 4-day MEA, three patients showed complete remission by other treatments, while the other three patients died of the disease. The major adverse effects were leukocytopenia, anemia, and nausea. Of 23 patients who were cured with 4-day MEA, treatment was changed to the etoposide and actinomycin D (EA) regimen in 14 patients, because of leukocytopenia, hepatotoxicity, and stomatitis. Among 20 patients who required hormonal therapy, 15 patients showed normal menstrual cycles after therapy. Five patients had nine conceptions (seven term live births and two spontaneous abortions). No babies were premature or had low birth weight nor did they have congenital anomalies. CONCLUSION: The results suggest that the efficacy and the adverse effects of 4-day MEA for choriocarcinoma and high-risk GTN may be the same level as EMA/CO. However, further study will be needed for determining the criteria of changing the treatment regimen from 4-day MEA to the EA regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Coriocarcinoma/tratamento farmacológico , Doença Trofoblástica Gestacional/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Dactinomicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Leucopenia/induzido quimicamente , Ciclo Menstrual/efeitos dos fármacos , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
6.
Mol Cell Endocrinol ; 498: 110583, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536780

RESUMO

In this study, we determined whether estragole and its isomer trans-anethole interfered with feto-placental steroidogenesis in a human co-culture model composed of fetal-like adrenocortical (H295R) and placental trophoblast-like (BeWo) cells. Estragole and trans-anethole are considered the biologically active compounds within basil and fennel seed essential oils, respectively. After a 24 h exposure of the co-culture to 2.5, 5.2 and 25 µM estragole or trans-anethole, hormone concentrations of estradiol, estrone, dehydroepiandrosterone, androstenedione, progesterone and estriol were significantly increased. Using RT-qPCR, estragole and trans-anethole were shown to significantly alter the expression of several key steroidogenic enzymes, such as those involved in cholesterol transport and steroid hormone biosynthesis, including StAR, CYP11A1, HSD3B1/2, SULT2A1, and HSD17B1, -4, and -5. Furthermore, we provided mechanistic insight into the ability of estragole and trans-anethole to stimulate promoter-specific expression of CYP19 through activation of the PKA pathway in H295R cells and the PKC pathway in BeWo cells, in both cases associated with increased cAMP levels. Moreover, we show new evidence suggesting a role for progesterone in regulating steroid hormone biosynthesis through regulation of the StAR gene.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Anisóis/farmacologia , Feto/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Placenta/metabolismo , Esteroides/metabolismo , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/patologia , Aromatase/genética , Aromatase/metabolismo , Sobrevivência Celular , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Técnicas de Cocultura , Estradiol Desidrogenases/genética , Estradiol Desidrogenases/metabolismo , Feminino , Feto/efeitos dos fármacos , Aromatizantes/farmacologia , Humanos , Óleos Voláteis/farmacologia , Placenta/efeitos dos fármacos , Gravidez , Células Tumorais Cultivadas
7.
Theranostics ; 9(15): 4354-4374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285766

RESUMO

Gestational trophoblastic neoplasia (GTN), the most aggressive form of which is choriocarcinoma, can result from over-proliferation of trophoblasts. Treating choriocarcinoma requires high doses of systemic chemotherapeutic agents, which result in nonspecific drug distribution and severe toxicity. To overcome these disadvantages and enhance chemotherapeutic efficacy, we synthesized redox- and pH-sensitive, self-assembling, ascorbic acid-derived (PEG-ss-aAPP) micelles to deliver the drug methotrexate (MTX). Methods: We developed and tested self-assembling PEG-ss-aAPP micelles, which release their drug cargo in response to an intracellular reducing environment and the acidity of the early lysosome or tumoral microenvironment. Uptake into JEG3 choriocarcinoma cancer cells was examined using confocal microscopy and transmission electron microscopy. We examined the ability of MTX-loaded PEG-ss-aAPP micelles to inhibit metastasis in an orthotopic mouse model of human choriocarcinoma. Results: Drug-loaded micelles had encapsulation efficiency above 95%. Particles were spherical based on transmission electron microscopy, with diameters of approximately 229.0 nm based on dynamic light scattering. The drug carrier responded sensitively to redox and pH changes, releasing its cargo in specific environments. PEG-ss-aAPP/MTX micelles efficiently escaped from lysosome/endosomes, and they were effective at producing reactive oxygen species, strongly inducing apoptosis and inhibiting invasion and migration. These effects correlated with the ability of PEG-ss-aAPP/MTX micelles to protect IκBα from degradation, which in turn inhibited translocation of NF-κB p65 to the nucleus. In an orthotopic mouse model of human choriocarcinoma, PEG-ss-aAPP/MTX micelles strongly inhibited primary tumor growth and significantly suppressed metastasis without obvious side effects. Conclusions: Our results highlight the potential of PEG-ss-aAPP micelles for targeted delivery of chemotherapeutic agents against choriocarcinoma.


Assuntos
Antineoplásicos/uso terapêutico , Ácido Ascórbico/química , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Metotrexato/uso terapêutico , Micelas , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Glutationa/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Metotrexato/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Metástase Neoplásica , Oxirredução , Polietilenoglicóis/química , Espectroscopia de Prótons por Ressonância Magnética , Espécies Reativas de Oxigênio/metabolismo , Succinimidas/química , Distribuição Tecidual/efeitos dos fármacos
8.
Anticancer Res ; 39(5): 2377-2383, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092430

RESUMO

BACKGROUND: Human choriocarcinoma is the most aggressive type of gestational trophoblastic neoplasia. The expression of epidermal growth factor receptor (EGFR) in choriocarcinomas is significantly higher than those of trophoblastic cells in healthy placentas. Lapatinib is a potent EGFR and human epidermal growth factor receptor 2 (HER2) inhibitor that inhibits cell proliferation and induces apoptosis in various human cancer cells. Amphiregulin (AREG) is the most abundant EGFR ligand in amniotic fluid during human pregnancy. AIM: To explore the role of AREG in human choriocarcinoma cell proliferation. MATERIALS AND METHODS: The effect of lapatinib and AREG on cell proliferation was examined by the MTT assay. Western blots were used to investigate EGFR and HER2 expression, and the activation of caspase-3, extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT) signaling pathways. RESULTS: Treatment with lapatinib reduced BeWo cell proliferation by inducing apoptosis. Moreover, AREG treatment stimulated BeWo cell proliferation by activating ERK1/2 and PI3K/AKT signaling pathways, which was blocked by lapatinib. CONCLUSION: Targeting EGFR/HER2 might be a useful therapeutic strategy for human choriocarcinoma.


Assuntos
Anfirregulina/genética , Coriocarcinoma/genética , Receptor ErbB-2/genética , Anfirregulina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Receptores ErbB/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lapatinib/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Oncogênica v-akt/genética , Receptor ErbB-2/antagonistas & inibidores
9.
J Cell Biochem ; 120(10): 16533-16542, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31081972

RESUMO

Choriocarcinoma is a gestational trophoblastic cancer, which often occurs in the first 3 months of pregnancy. 5-Fluorouracil (5-Fu) is the widely used chemotherapeutic drug for choriocarcinoma but limited by drug resistance. Lidocaine, an aminamide-type anesthetic, shows potential anticancer and chemosensitization effects in recent years. Herein, we tested the possible chemosensitization activity of lidocaine on the cytotoxicity of 5-Fu in choriocarcinoma cells. Viabilities and apoptosis of choriocarcinoma JEG-3 and JAR cells after lidocaine and/or 5-Fu treatment were detected using Cell Counting Kit-8 assay, annexin V-FITC/PI (fluorescein isothiocyanate/propidium iodide) staining and Western blot analysis, respectively. Quantitative reverse transcription polymerase chain reaction was done to measure breast cancer resistance protein (ABCG2) messenger RNA level. Western blot analysis was carried out to detect ABCG2, P-glycoprotein (P-gp), MRP1, and MRP2 protein levels. pEX-ABCG2 was transfected to elevate ABCG2 level. Then, the influence of ABCG2 on lidocaine + 5-Fu-caused cell viability loss, apoptosis, and inactivation of PI3K/AKT pathway were analyzed. We found that lidocaine in low concentration had no significant cytotoxicity to JEG-3 and JAR cells, but stimulated cell apoptosis in high concentration. Moreover, lidocaine potentiated the cytotoxicity of 5-Fu to JEG-3 and JAR cells through decreasing viability and increasing apoptosis. Lidocaine treatment reduced the ABCG2, P-gp, MRP1, and MRP2 protein levels in cells. Overexpression of ABCG2 reversed the synergistic effects of lidocaine + 5-Fu on JEG-3 and JAR cell viability and apoptosis, as well as PI3K/AKT pathway. Our research verified that lidocaine potentiated the cytotoxicity of 5-Fu to choriocarcinoma cells by downregulating ATP-binding cassette (ABC) transport proteins expression.


Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Coriocarcinoma/metabolismo , Citotoxinas/farmacologia , Regulação para Baixo/efeitos dos fármacos , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lidocaína/farmacologia , Proteínas de Neoplasias/biossíntese , Linhagem Celular Tumoral , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Humanos
10.
J Cell Biochem ; 120(9): 15131-15144, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31020694

RESUMO

Choriocarcinoma (CC) is a trophoblast tumor prone to early distant organ metastases. At present, the main treatment for CC is chemotherapy, but chemotherapy resistance readily occurs and leads to treatment failure. H19 is a long noncoding RNA, and its abnormal expression has been found in various tumors, including CC. H19 is also considered to be related to the drug resistance mechanism of the same cancers. To investigate the role of H19 in drug-resistant CC cells, the following experiments were designed. We used human CC cell line JEG-3 to establish cell lines resistant to methotrexate and 5-fluorouracil (JEG-3/MTX and JEG-3/5-FU) and detected the expression of H19 in JEG-3, JEG-3/MTX, JEG-3/5-FU cells, JEG-3 with MTX, and JEG-3 with 5-FU. We found that the expression of H19 in the JEG-3/MTX and JEG-3/5-FU cells were significantly higher than that in JEG-3 cells. JEG-3 cells were treated with MTX or 5-FU for and quantitative real-time polymerase chain reaction assay revealed that H19 messenger RNA expression increased. Furthermore, after H19 was knocked out, the drug resistance index of the JEG-3/MTX and JEG-3/5-FU cells decreased; the proliferation, migration, and invasion ability diminished significantly; and apoptosis increased significantly. Finally, we detected the total and phosphorylation protein expression of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in the JEG-3/MTX and JEG-3/5-FU cells. The total protein of PI3K, AKT, and mTOR in the H19 knockout resistant cells showed no significant change relative to those in the H19 non-knockout resistant cells, whereas the phosphorylated proteins of PI3K, AKT, and mTOR were significantly decreased. Phosphorylated proteins of PI3K, AKT, and mTOR in the JEG-3/MTX and JEG-3/5-FU cells were significantly higher than that in JEG-3 cells. After using inhibition of phosphorylated PI3K/AKT/mTOR, the proliferation, migration, and invasion ability of the JEG-3/MTX and JEG-3/5-FU cells diminished significantly; and apoptosis increased significantly. On the basis of the above experiments, we concluded that H19 is related to the drug resistance of CC, and the knockout of H19 can reduce the drug resistance of resistant CC cells; and decrease the proliferative, migratory, and invasive ability; and increase the apoptosis. PI3K/AKT/mTOR pathway might be involved in H19-mediated effects. H19 is expected to be a therapeutic target for the treatment of drug-resistant chorionic carcinoma.


Assuntos
Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/genética , Resistencia a Medicamentos Antineoplásicos/genética , RNA Longo não Codificante/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Coriocarcinoma/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Concentração Inibidora 50 , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Cicatrização/efeitos dos fármacos
11.
Biomater Sci ; 7(3): 1200-1210, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30656300

RESUMO

To investigate whether circulating tumor cells (CTCs) are detectable in patients with gestational choriocarcinoma (GC) and evaluate the prognostic value of CTC enumeration. In this multicenter study, the presence of CTCs was examined in 180 GC patients using a semi-automated NanoVelcro system, among whom 106 patients underwent CTC re-evaluation after one cycle of chemotherapy. Approximately 96% of the GC patients contained ≥2 CTCs in 7.5 mL of blood. The number of CTCs per 7.5 mL of blood was much higher in patients with distant metastases (n = 95; range, 0 to 104) than in patients without distant metastases (n = 85; range, 0 to 6). Applying a 90-patient training and 90-patient validation cohort, a cutoff value of ≥6 CTCs was defined as the prognostic threshold for progression-free survival (PFS) and overall survival (OS). The presence of ≥6 CTCs was significantly associated with worse PFS and OS (both P < 0.001). A multivariate analysis showed that the CTC number (≥6 CTCs) was the strongest predictor of OS (hazard ratio [HR], 15.8; 95% confidence interval [CI], 4.3-57.9; P < 0.001). The number of CTCs decreased after one cycle of chemotherapy; univariate analyses demonstrated that the CTC count after the first chemotherapy cycle was a strong predictor of OS (HR, 36.1; 95% CI, 4.8-271.5; P < 0.001). CTCs are a promising prognostic factor for GC. The absolute CTC count after one cycle of chemotherapy in the context of this disease is a strong predictor of chemotherapy response.


Assuntos
Neoplasias da Mama/patologia , Coriocarcinoma/patologia , Células Neoplásicas Circulantes/química , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Basigina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/mortalidade , Molécula de Adesão da Célula Epitelial/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Fatores de Risco
12.
Med J Malaysia ; 74(6): 504-508, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31929476

RESUMO

INTRODUCTION: Choriocarcinoma is malignant cancer originating from placental trophoblast. The incidence of this cancer is estimated at 0.57-1.1 per 1000 births in the United States of America, Australia, Europe, and New Zealand. The rate is much higher in South East Asia and Japan with two occurrences per a thousand births. Telomerase activity is an important part of the apoptotic process. Increased telomerase activity will result in cellular immortality and poor prognosis in cancer. Vitamin A possess an essential role in cell proliferation and differentiation. One of the active metabolites of vitamin A is All-Trans Retinoic Acid (ATRA). METHODS: In this study, we examined the role of ATRA against telomerase activity in choriocarcinoma cell. This cell was derived from BeWo cell line (ATCC CCL-98) and were given different doses of ATRA. RESULTS: From this study, Choriocarcinoma cell that was given ATRA in dosage of 50µg/ml inhibit telomerase activity by extending the cycle time of 39.51±0.09, compared to the control group with a cycle time of 37.62±0.43. Cycle length change consistently with higher dose of ATRA. CONCLUSION: This study has proven that ATRA could inhibit telomerase activity by lengthening the cycle. Changes in the increase of ATRA doses in this experimental test need to be studied further on experimental animals, either administered as a single agent or as an addition to standard treatment of trophoblastic disease.


Assuntos
Coriocarcinoma/tratamento farmacológico , Telomerase/antagonistas & inibidores , Tretinoína/administração & dosagem , Neoplasias Uterinas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Biomarcadores Tumorais/biossíntese , Diferenciação Celular/efeitos dos fármacos , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Gravidez , Telomerase/biossíntese , Células Tumorais Cultivadas , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
13.
Int J Cancer ; 144(6): 1421-1431, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30070688

RESUMO

Gestational choriocarcinoma (GC) is a highly aggressive tumor. In our study, we systematically investigated EpCAM/CD147 expression characteristics in patients with GC and assessed the role of circulating tumor cells (CTCs) in predicting chemotherapy response and disease progression. GC tissues were positive for either epithelial cellular adhesion molecule (EpCAM) or CD147, and all samples exhibited strong human chorionic gonadotropin (HCG) expression. Among all the recruited patients (n = 115), 103 had at least 1 CTC in a 7.5-mL peripheral blood sample, and the percentage of patients with ≥4 CTCs in a particular FIGO stage group increased with a higher FIGO stage (p < 0.001). Furthermore, the pretreatment CTC count was related to tumor size (r = 0.225, p = 0.015) and the number of metastases (r = 0.603, p < 0.001). A progression analysis showed that among the 115 included patients who qualified for further examination, 52 of the 64 patients defined as progressive had ≥4 pretreatment CTCs, while only 7 of the 51 non-progressive patients had ≥4 pretreatment CTCs (p < 0.001). In multivariate analysis, CTCs (≥4) remained the strongest predictor of PFS when other prognostic markers, FIGO score and FIGO stage were included. Moreover, based on the chemotherapy response, patients with ≥4 CTCs were more likely to be resistant to chemotherapy than those with <4 CTCs (P < 0.001). These findings demonstrates the feasibility of CTC detection in cases of GC by adopting EpCAM/CD147 antibodies together as capturing antibodies. The CTC count is a promising indicator in the evaluation of biological activities and the chemotherapy response in GC patients.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Coriocarcinoma/sangue , Resistencia a Medicamentos Antineoplásicos , Células Neoplásicas Circulantes , Adulto , Antineoplásicos/uso terapêutico , Basigina/metabolismo , Biópsia , Contagem de Células , Linhagem Celular Tumoral , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/mortalidade , Coriocarcinoma/patologia , Gonadotropina Coriônica/metabolismo , Progressão da Doença , Molécula de Adesão da Célula Epitelial/metabolismo , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Fatores de Risco , Adulto Jovem
14.
J Cell Physiol ; 234(2): 1803-1815, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30070691

RESUMO

Carvacrol is a monoterpenoid phenol present in the oils of various plants including Origanum vulgare (oregano) or Origanum majorana (marjoram). For a long time, it has been used as spice in foods because of its antimicrobial properties. Additionally, it appears to have anticancer effects against some cancer but this has not been well studied. Therefore, we conducted various assays to confirm the effects of carvacrol on choriocarcinoma cell lines (JAR and JEG3). Our results indicate that carvacrol has antiproliferative properties and induces apoptosis, resulting in increased expression of proapoptotic proteins. Additionally, carvacrol disrupted the mitochondrial membrane potential and induced calcium ion overload in the mitochondrial matrix in both JAR and JEG3 cells. Furthermore, carvacrol generated oxidative stress and lipid peroxidation in both JAR and JEG3 cells. Moreover, carvacrol-suppressed phosphoinositide 3-kinase-protein kinase B and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (MAPK) signal transduction whereas expression of phosphor-P38 and c-Jun N-terminal kinase MAPK was increased. Together, our results indicate that carvacrol may be a possible new therapeutic agent or supplement for the control of human choriocarcinomas.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Coriocarcinoma/tratamento farmacológico , Cimenos/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias Uterinas/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Feminino , Homeostase , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
15.
Obstet Gynecol ; 133(1): 163-166, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30531566

RESUMO

BACKGROUND: Gestational trophoblastic neoplasia rarely occurs in term pregnancies. Stage IV choriocarcinoma treated with conventional chemotherapy can result in death as a result of hemorrhagic sequelae at tumor sites. CASE: A 30-year-old woman at 34 weeks of gestation presented with a persistent cough, worsening dyspnea, and vaginal bleeding. Chest radiograph demonstrated innumerable lung nodules, and quantitative ß-hcg concentration exceeded 1.3 million milli-international units/mL. Cesarean delivery was performed for presumed abruption. Placental pathology demonstrated choriocarcinoma, and imaging confirmed stage IV disease with a World Health Organization score of 14. Remission was achieved after two courses of low-dose induction chemotherapy followed by 10 cycles of combination chemotherapy. CONCLUSION: Gestational trophoblastic neoplasia should be considered in a pregnant or postpartum woman presenting with atypical vaginal bleeding. Coexistent pulmonary or neurologic findings may suggest advanced disease.


Assuntos
Coriocarcinoma/diagnóstico , Doença Trofoblástica Gestacional/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Diagnóstico Pré-Natal , Neoplasias Uterinas/diagnóstico , Adulto , Antineoplásicos/uso terapêutico , Coriocarcinoma/complicações , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/secundário , Diagnóstico Diferencial , Feminino , Doença Trofoblástica Gestacional/complicações , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/secundário , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Gravidez , Terceiro Trimestre da Gravidez , Hemorragia Uterina/etiologia , Neoplasias Uterinas/complicações , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia
16.
Arch Gynecol Obstet ; 299(4): 1115-1119, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30569343

RESUMO

BACKGROUND AND PURPOSE: Choriocarcinoma (CCA) is a rare form of malignant trophoblastic disease. Systemic polychemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) is the mainstay of treatment for metastatic disease. Due to the rarity of the condition, however, the evidence basis for this management is small and other chemotherapy regimens may also be effective. The reported case presents anecdotal evidence of an effective etoposide monotherapy treatment. METHOD: CASE PRESENTATION: We report the case of a patient with gestational choriocarcinoma and pulmonary metastases initially treated with methotrexate. Due to local disease progression, she underwent hysterectomy and continued treatment with methotrexate. After pulmonary progression, she was switched to oral etoposide. RESULTS: After four cycles of etoposide monotherapy at a oral dosage of 100 mg d1-7, q28, the patient had no evidence of disease according to human chorionic gonadotropin serum levels and imaging studies. The treatment was well tolerated with World Health Organization (WHO) grade 2 alopecia and hot flushes as the most prominent side effects. The patient has achieved a sustained complete remission with a follow-up of 6 years. CONCLUSION: Oral etoposide may be an effective treatment alternative to EMA/CO in selected patients with oligometastatic CCA.


Assuntos
Coriocarcinoma/tratamento farmacológico , Etoposídeo/uso terapêutico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Coriocarcinoma/patologia , Feminino , Humanos , Metástase Neoplásica , Guias de Prática Clínica como Assunto , Gravidez , Neoplasias Uterinas/patologia
17.
Int J Clin Oncol ; 24(2): 153-160, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30242539

RESUMO

OBJECTIVE: To evaluate the survival and functional outcome of patients with brain metastasis due to gestational trophoblastic neoplasia (GTN). METHODS: A 17-year retrospective study based on case review of women with brain metastasis from GTN identified by the electronic databases held in the French Reference Centre. PRIMARY OUTCOME MEASURE: 5-year overall survival calculated with the Kaplan-Meier method. SECONDARY OUTCOME MEASURES: causes of death, prognostic factors and functional outcomes. RESULTS: 21 patients had GTN brain metastasis and were treated with multidrug chemotherapy without concomitant whole-brain radiation therapy. Three patients died early (< 4 weeks) of cerebral hemorrhage, 3 died ≥ 1 months after treatment initiation and 15 were alive at the date of last contact. The overall survival rate at 5 years was 69.8% (95% CI 44.3-85.3). After excluding early deaths, the survival rate at 5 years was 81.5% (95% CI 52.3-93.7). No predictive factor of survival was identified. Although 11 of the 12 (92%) surviving patients contacted still reported sequelae, nine of them (75%) had resumed a normal life. CONCLUSIONS: After excluding early deaths, this study implies a high survival rate in patients with brain metastasis from GTN. These results were achieved in the total absence of whole-brain radiotherapy and almost completely without the need for intrathecal methotrexate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Coriocarcinoma/patologia , Doença Trofoblástica Gestacional/patologia , Neoplasias Uterinas/patologia , Adolescente , Adulto , Neoplasias Encefálicas/tratamento farmacológico , Coriocarcinoma/tratamento farmacológico , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Gravidez , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias Uterinas/tratamento farmacológico , Adulto Jovem
18.
Phytomedicine ; 50: 238-246, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30466984

RESUMO

BACKGROUND: Human placental choriocarcinoma is a gestational trophoblastic tumor with high rates of metastasis and reoccurrence. However, some patients with choriocarcinoma are chemoresistance to conventional chemotherapeutic agents. HYPOTHESIS: Naringenin increases apoptosis in human placental choriocarcinoma cells. METHODS: We investigated the effects of naringenin on proliferation and migration of JAR and JEG3 cells, and performed TUNEL and Annexin V/PI staining assays to examine apoptotic effects of naringenin on both cells. In addition, we studied the loss of mitochondrial membrane potential (MMP) and the production of mitochondrial reactive oxygen species (ROS) to determine the specific reason for apoptosis of choriocarcinoma cells being mediated via mitochondria. Consistent with the induction of production of ROS by naringenin in both choriocarcinoma cell lines, we investigated lipid peroxidation and glutathione levels in both JAR and JEG3 cells since both are affected by ROS. We next determined dose-dependent effects of naringenin and its pharmacological inhibitors on signal transduction pathways in JAR and JEG3 cells by western blot analyses. RESULTS: Naringenin reduced viability and migratory functions of both cell lines, and increased mitochondria related apoptosis induced by ROS and lipid peroxidation, decreased glutathione and decreased mitochondrial membrane potential MMP in a dose-dependent manner. We also determined naringenin activated phosphorylation of ERK1/2, P38, JNK and P70S6K in JAR and JEG3 cells in a dose-response manner. Although naringenin induced phosphorylation of AKT proteins in JAR cells, it suppressed phosphorylation of the protein in JEG3 cells. In addition, we confirmed the mechanism of naringenin-induced cell signaling by using a combination of naringenin and pharmacological inhibitors of the PI3K and MAPK pathways, as well as a ROS inhibitor in JAR and JEG3 cell lines. CONCLUSIONS: Collectively, results of this study indicate that naringenin is a potential therapeutic molecule with anti-cancer effects on choriocarcinoma cells by inducing generation of ROS and activation of the MAPK pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Coriocarcinoma/patologia , Flavanonas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Coriocarcinoma/tratamento farmacológico , Feminino , Humanos , MAP Quinase Quinase 4/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo
19.
Int J Mol Sci ; 19(11)2018 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-30400387

RESUMO

Tripyrrole molecules have received renewed attention due to reports of numerous biological activities, including antifungal, antibacterial, antiprotozoal, antimalarial, immunosuppressive, and anticancer activities. In a screen of bacterial strains with known toxicities to termites, a red pigment-producing strain, HDZK-BYSB107, was isolated from Chamaecyparis lawsoniana, which grows in Oregon, USA. Strain HDZK-BYSB107 was identified as Serratia marcescens subsp. lawsoniana. The red pigment was identified as prodigiosin using ultraviolet absorption, LC-MS, and 1H-NMR spectroscopy. The bacterial prodigiosin had an inhibitory effect on both Gram-negative and Gram-positive bacteria. The main objective of this study was to explore the anticancer activities and mechanism of strain HDZK-BYSB107 prodigiosin by using human choriocarcinoma (JEG3) and prostate cancer cell lines (PC3) in vitro and JEG3 and PC3 tumor-bearing nude mice in vivo. In vitro anticancer activities showed that the bacterial prodigiosin induced apoptosis in JEG3 cells. In vivo anticancer activities indicated that the prodigiosin significantly inhibited the growth of JEG3 and PC3 cells, and the inhibitory activity was dose and time dependent. The anticancer efficacy of the bacterial prodigiosin on JEG3 and PC3 cells, JEG3 and PC3 tumor exhibited a correlation with the down regulation of the inhibitor of IAP family, including XIAP, cIAP-1 and cIAP-2, and the activation of caspase-9 and caspase-3 accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. The expressions of P53 and Bax/Bcl-2 in JEG3 and PC3 cells were significantly higher than in untreated groups. Our results indicated that the bacterial prodigiosin extracted from C. lawsoniana is a promising molecule due to its potential for therapeutic applications.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Coriocarcinoma/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Prodigiosina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Serratia marcescens/química , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Proteína 3 com Repetições IAP de Baculovírus/genética , Proteína 3 com Repetições IAP de Baculovírus/metabolismo , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular Tumoral , Coriocarcinoma/genética , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Camundongos Nus , Testes de Sensibilidade Microbiana , Células PC-3 , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Prodigiosina/biossíntese , Prodigiosina/isolamento & purificação , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serratia marcescens/metabolismo , Carga Tumoral/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
20.
Cell Physiol Biochem ; 50(5): 1815-1831, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30396168

RESUMO

BACKGROUND/AIMS: Choriocarcinoma (CC) is a highly aggressive gestational trophoblastic neoplasia; however, the underlying molecular mechanisms of its invasiveness and metastasis remain poorly understood. Human secreted frizzled-related protein 2 (SFRP2) could function as a tumor promoter or suppressor in different tumors, yet the role it plays in CC's invasion and metastasis is thoroughly unclear. The current study was aimed to explore the function and underlying mechanism of SFRP2 in CC. METHODS: The expression of SFRP2 in CC tissues was examined via immunohistochemistry. The methylation level and expression of SFRP2 in CC cell lines, JEG-3 and JAR were examined via bisulfite sequencing PCR (BSP), western blotting and quantitative RT-PCR. The biological role of increasing expressed SFRP2 through its promoter demethylation with 5-Aza-2'-deoxycytidine (5-Aza) was examined by a series of in vitro functional studies. Furthermore, lentivirus transfection technology was adopted to investigate the biological roles of SFRP2 knockdown in JEG-3 and JAR cells in vitro and in vivo. Moreover, its downstream signaling pathway was investigated. RESULTS: SFRP2 was downregulated in CC tissues, and its expression was inversely related to its promoter hypermethylation frequency in JEG-3 and JAR cells. Increased SFRP2 through its promoter demethylation inhibited cell migration, invasion and colony formation in JEG-3 and JAR cells, whereas decreased SFRP2 reversed the epithelial-mesenchymal transition (EMT) process and stemness in JEG-3 and JAR cells both in vitro and vivo. Mechanistically, SFRP2 regulated the EMT and stemness of CC cell lines via canonical Wnt/ß-catenin signaling, validated by the usage of a Wnt activator and inhibitor. CONCLUSION: The current study indicates that downregulated SFRP2 has potent tumor-promotive effects in CC through the modulation of cancer stemness and the EMT phenotype via activation of Wnt/ß-catenin signaling in vitro and in vivo.


Assuntos
Transição Epitelial-Mesenquimal , Proteínas de Membrana/metabolismo , Via de Sinalização Wnt , Animais , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/metabolismo , Coriocarcinoma/patologia , Metilação de DNA , Decitabina , Proteínas Desgrenhadas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Camundongos Nus , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
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