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1.
Appl. cancer res ; 40: 1-9, Oct. 19, 2020. ilus, tab
Article in English | LILACS, Inca | ID: biblio-1281398

ABSTRACT

Background: Ovarian cancer is the most common gynecological malignancy. In patients with advanced ovarian cancer, some biological parameters have prognostic implementations. P27kip1 is an inhibitor of a cycline-dependent kinase, its loss, can contribute to tumor progression. Objective: This study aimed to examine the importance of P27KIP1 protein in predicting the prognosis and response to neoadjuvant chemotherapy in patients with advanced ovarian epithelial cancer and to compare the outcomes of immunohistochemistry with Quantitative Real-time PCR. Patients and methods: We have studied P27KIP1expression by both immunohistochemistry and Quantitative Realtime PCR from 88 patients with advanced ovarian carcinomas undergone radical debulking surgery and received Paclitaxel followed by Cisplatin every 3 weeks for a total of 6 cycles. We also studied their association with both chemotherapy response and patient survival. Results: Nuclear expression of p27KIP1 protein was intense in 86 normal ovarian tissues and 42 of 88 carcinomas. The P27kip1mRNA expression level by qRT-PCR was very low in ovarian cancer tissues relative to its adjacent normal tissues. The results were statistically significant by both methods of determination. p27KIP1 expression was significantly related to good prognostic parameters as low stage tumors, differentiated tumors, absence of ascites, residual disease < 2 cm, and response to chemotherapy but not with histopathological type in case of determination by immunohistochemistry. Comparison of P27kip1 by both immunohistochemistry and qRTPCR with different prognostic parameters revealed no significant difference between both methods in the assessment of these parameters. In 4 years of follow-up, 20.5% of patients were alive without evidence of disease. 6.8% were alive with disease. The disease-related four -year survival rate for the whole group was 28.2%. In multivariate analysis, residual disease, histological type, tumor differentiation, ascites was of independent prognostic significance. Conclusion: In ovarian cancer, patients with loss of p27KIP1 expression are at a greater likelihood of disease progression, p27KIP1 may be used as a molecular marker to predict response to chemotherapy and prognosis. Both immunohistochemistry and qRT-PCR have equal reliability in the determination of p27 KIP1


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Young Adult , Ovarian Neoplasms/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Carcinoma, Ovarian Epithelial/metabolism , Ovarian Neoplasms/drug therapy , Prognosis , Immunohistochemistry , Neoadjuvant Therapy , Real-Time Polymerase Chain Reaction , Carcinoma, Ovarian Epithelial/drug therapy , Neoplasm Staging
2.
Med. leg. Costa Rica ; 37(1): 54-61, ene.-mar. 2020. tab
Article in Spanish | LILACS | ID: biblio-1098372

ABSTRACT

Resumen El cáncer de ovario se ha caracterizado por ser la neoplasia ginecológica de peor pronóstico. Lo anterior es consecuencia del curso silente de la enfermedad que ocasiona que la mayoría de las veces el diagnóstico se realice en etapas avanzadas. La información recolectada señala que los avances terapéuticos no han demostrado ser efectivos en mejorar la sobrevida de las pacientes con cáncer de ovario, lo cual orienta a la búsqueda constante de un método (o conjunto de éstos), que permita llevar a cabo el tamizaje y la detección temprana de dicha patología. Sin embargo, debido a que actualmente no se ha logrado identificar un método que sea costo-efectivo para el tamizaje, el mismo no se aplica a la población general y se reserva para casos específicos, como mujeres con antecedentes familiares de la enfermedad o que presentan síndromes hereditarios. Esta revisión incluye además información sobre las diferentes técnicas de imagen utilizadas tanto para el estudio y caracterización de masas anexiales, como para el estadiaje y pronóstico del cáncer de ovario. De las técnicas estudiadas, el ultrasonido (US) demostró ser la mejor opción para el abordaje inicial de masas anexiales; sin embargo, a la hora de realizar el estadiaje resultó ser inferior a la tomografía computarizada (TC) y la resonancia magnética (RM).


Abstract Ovarian cancer is the gynecological malignancy with the worst prognosis. Due to the silent course of the disease the diagnosis is made mainly in advanced stages. The literature reviewed showed that the therapeutic advances have not shown any major improvement in patient´s survival with ovarian cancer, therefore there is a constant research for a technique (or a set of them) that allows a proper screening and early detection of the disease. However, a cost effective method has not been found for screening, therefore it is not recommended for general population and it is reserved for specific cases, such as women with family history of ovarian cancer and with hereditary syndromes. This review also includes information about the different imaging techniques available not only for the study and characterization of neoplasms, but also for staging and prognosis of ovarian cancer. The ultrasound proved to be the best option for the initial approach of adnexal masses, however it has shown to be inferior for staging than CT-Scan and MRI.


Subject(s)
Female , Ovarian Neoplasms/diagnostic imaging , Carcinoma, Ovarian Epithelial/diagnostic imaging , Ovarian Neoplasms/drug therapy , Ultrasonics/instrumentation
3.
Braz. j. med. biol. res ; 53(6): e8885, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132519

ABSTRACT

In this study, we aimed to analyze the anti-cancer effects of β-elemene combined with paclitaxel for ovarian cancer. RT-qPCR, MTT assay, western blot, flow cytometry, and immunohistochemistry were used to analyze in vitro and in vivo anti-cancer effects of combined treatment of β-elemene and paclitaxel. The in vitro results showed that β-elemene+paclitaxel treatment markedly inhibited ovarian cancer cell growth, migration, and invasion compared to either paclitaxel or β-elemene treatment alone. Results demonstrated that β-elemene+paclitaxel induced apoptosis of SKOV3 cells, down-regulated anti-apoptotic Bcl-2 and Bcl-xl gene expression and up-regulated pro-apoptotic P53 and Apaf1 gene expression in SKOV3 cells. Administration of β-elemene+paclitaxel arrested SKOV3 cell cycle at S phase and down-regulated CDK1, cyclin-B1, and P27 gene expression and apoptotic-related resistant gene expression of MDR1, LRP, and TS in SKOV3 cells. In vivo experiments showed that treatment with β-elemene+paclitaxel significantly inhibited ovarian tumor growth and prolonged the overall survival of SKOV3-bearing mice. In addition, the treatment inhibited phosphorylated STAT3 and NF-κB expression in vitro and in vivo. Furthermore, it inhibited migration and invasion through down-regulation of the STAT-NF-κB signaling pathway in SKOV3 cells. In conclusion, the data suggested that β-elemene+paclitaxel can inhibit ovarian cancer growth via down-regulation of the STAT3-NF-κB signaling pathway, which may be a potential therapeutic strategy for ovarian cancer therapy.


Subject(s)
Animals , Male , Female , Rabbits , Ovarian Neoplasms/drug therapy , Sesquiterpenes/administration & dosage , Cell Movement/drug effects , NF-kappa B/adverse effects , Paclitaxel/administration & dosage , Apoptosis/drug effects , Cell Proliferation/drug effects , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Immunohistochemistry , Transfection , Signal Transduction , Blotting, Western , NF-kappa B/metabolism , Cell Line, Tumor , Real-Time Polymerase Chain Reaction , Mice, Inbred BALB C
4.
Article in Chinese | WPRIM | ID: wpr-880796

ABSTRACT

OBJECTIVE@#To investigate the effect of interleukin-17A (IL-17A) on chemosensitivity of ovarian cancer cells to cisplatin (DDP) and explore the mechanism in light of autophagy regulation.@*METHODS@#Ovarian cancer SKOV3 cells cultured @*RESULTS@#DDP increased the expression of IL-17RA in ovarian cancer SKOV3 cells. Treatment with IL-17A significantly reduced the susceptibility of SKOV3 cells to cisplatin-induced apoptosis (@*CONCLUSIONS@#IL-17A/IL-17RA can decrease chemosensitivity of SKOV3 cells to DDP by upregulating DDP-induced autophagy.


Subject(s)
Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Female , Humans , Interleukin-17/pharmacology , Ovarian Neoplasms/drug therapy , Receptors, Interleukin-17
5.
Biol. Res ; 52: 13, 2019. graf
Article in English | LILACS | ID: biblio-1011415

ABSTRACT

BACKGROUND: Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780. METHODS: The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 µM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 µM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells. RESULTS: Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions. CONCLUSION: CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/3-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.


Subject(s)
Humans , Female , Ovarian Neoplasms/genetics , Gene Expression Regulation, Neoplastic/drug effects , Carboplatin/pharmacology , Drug Resistance, Neoplasm/genetics , Transcriptome/drug effects , Antineoplastic Agents/pharmacology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Phenotype , Signal Transduction , Cell Death/drug effects , Cell Death/genetics , Sequence Analysis, RNA , Cell Line, Tumor , Transcriptome/genetics
6.
Braz. arch. biol. technol ; 62: e19180531, 2019. tab, graf
Article in English | LILACS | ID: biblio-1039123

ABSTRACT

Abstract Natural products, especially phytochemicals, have been extensively studies and have exhibited important antiproliferative effects. The American native species Urera baccifera (L.) Gaudich. ex Wedd. (Urticaceae) is widely distributed in Brazil, where it is known as urtiga-vermelha or urtigão. The leaves are popularly used as anti-inflammatory, antirheumatic and in the treatment of gastric disorders. However, the antiproliferative potential of this plant against human tumor cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of U. baccifera leaves extracts and fractions against a panel of human tumor cell lines in vitro besides a chemical evaluation of the most active sample by mass spectrometry (ESI-IT-MSn). The hydroalcoholic extract was inactive while dichloromethane extract showed moderate cytostatic activity against ovarian carcinoma cell line (OVCAR-3, GI50 = 1.5 μg/mL). More, the ethyl acetate and n-butanol fractions did not show important activity against tumour cell while the dichloromethane and hexane fractions showed moderate cytostatic activity against ovarian tumor cell line (OVCAR-3, GI50 = 12.7 and 9.4 μg/mL, respectively). Finally, the chemical profile evaluated by mass spectrometry (ESI-IT-MSn) allowed the detection of flavonoids in the HEU and hydroxylated fatty acid in DEU that can explain partially the biological effects observed. This is the first report of the antiproliferative effects of U. baccifera, and DEU has shown potential as a promising source of bioactive compounds.


Subject(s)
Ovarian Neoplasms/drug therapy , Plants, Medicinal/drug effects , Chemical Phenomena/drug effects , Antineoplastic Agents/pharmacology , Mass Spectrometry/instrumentation
7.
Article in Portuguese | LILACS | ID: biblio-1047557

ABSTRACT

Introdução: Drogas antineoplásicas neurotóxicas estão frequentemente associadas à neuropatia periférica induzida por quimioterapia (NPIQ). Objetivo: Avaliar a evolução clínica dos pacientes expostos a tratamento antineoplásico potencialmente neurotóxico e identificar possíveis preditores clínicos e sociodemográficos para o desenvolvimento da NPIQ. Método: Estudo de coorte prospectiva com pacientes com diagnóstico de câncer de mama, ovário ou intestino em tratamento quimioterápico com paclitaxel, docetaxel ou oxaliplatina. Foram avaliados antes da quimioterapia (T1), no terceiro mês (T2) e 30-60 dias após interrupção do tratamento (T3). Todos responderam ao questionário de perfis sociodemográfico e clínico, foram avaliados por meio de exame clínico neurológico, pela escala de performance ECOG, escala hospitalar de ansiedade e depressão (HAD), escala de dor Short-cGuill, autorrelato de sintomas de NPIQ e avaliação com o questionário de neurotoxicidade induzida por antineoplásicos (CINQ). Resultados: Por meio de autorrelato, 75% da dos pacientes informaram apresentar sintomas de NPIQ. O CINQ evidenciou que 90% apresentaram algum grau de NPIQ em T2, enquanto 82,5% ainda persistiam em T3. Dor neuropática acometeu 42% da população (RR=1,429; IC95%=1,130-1,806). Os escores de ansiedade e depressão reduziram significativamente quando comparados ao início de tratamento (redução de 2,5 pontos na escala HAD, p<0,05). A capacidade funcional da população não mostrou alterações significativas. No T2, a escolaridade foi considerada preditora para autorrelato de sintomas de NPIQ (OR=1,314, IC95%=1,002-1,723, p=0,048). Conclusão:A baixa escolaridade pode comprometer a capacidade do paciente em relatar os sintomas da NPIQ. Este estudo chama a atenção para a necessidade de utilização de instrumentos específicos para detecção precoce da NPIQ.


Introduction: Neurotoxic antineoplastic drugs are frequently associated to chemotherapy-induced peripheral neuropathy (CIPN). Objective: To evaluate the clinical evolution of patients exposed to potentially neurotoxic antineoplastic treatment and to identify possible clinical and sociodemographic predictors for the development of CIPN. Method: Cohort prospective study with patients with breast, ovary or intestine diagnosis of cancer in chemotherapy treatment with paclitaxel, docetaxel or oxaliplatin. They were assessed before the chemotherapy (T1), in the third month (T2) and 30-60 days after the interruption of the treatment (T3). All the patients responded to the questionnaire of clinical and sociodemographic profiles, were evaluated through neurologic clinical exam, by the performance scale ECOG, by the Hospital Anxiety and Depression Scale - HAD, pain scale of Short-cGuill, self-report of symptoms of CIPN and evaluation with the questionnaire of antineoplastic-induced neurotoxicity (QAIN). Results: Through self-report, 75% of the patients presented symptoms of CIPN. The QAIN showed that 90% presented a certain degree of CIPN in T2, while 82.5% still persisted in T3. Neuropathic pain affected 42% of the population (RR = 1.429, CI95% = 1.130-1.806). Anxiety and depression scores significantly reduced when compared with the beginning of the treatment (reduction of 2.5 points in the scale HAD, p < 0.05). The functional capacity of the population did not show any significant change. The school level was considered a predictor of self-report of CIPN symptoms in T2 (OR = 1.314, CI95% = 1.002-1.723, p = 0.048). Conclusion: The low school level may taint the patient capacity to report CIPN symptoms. This study draws attention for the necessity to use specific instruments for early detection of CIPN.


Introducción: Los fármacos antineoplásicos neurotóxicos a menudo se asocian con neuropatía periférica inducida por quimioterapia (CIPN). Objetivo: Evaluar la evolución clínica de pacientes expuestos a tratamientos antineoplásicos potencialmente neurotóxicos e identificar posibles predictores clínicos y sociodemográficos para el desarrollo de CIPN. Método: Estudio de cohorte prospectivo con pacientes diagnosticadas con cáncer de mama, ovario o intestino sometidos a quimioterapia con paclitaxel, docetaxel u oxaliplatino. Se evaluaron antes de la quimioterapia (T1), en el tercer mes (T2) y 30-60 días después de la interrupción del tratamiento (T3). Todos respondieron el cuestionario de perfil sociodemográfico y clínico, se evaluaron mediante un examen neurológico clínico, la escala de rendimiento ECOG, la escala de ansiedad y depresión hospitalaria (HAD), la escala de dolor Short-cGuill, el autoinforme de los síntomas de CIPN y la evaluación con el cuestionario de neurotoxicidad inducida por antineoplásicos (CINQ). Resultados: Por autoinforme, el 75% de la población informó presentar síntomas de CIPN. El CINQ mostró que el 90% tenía algún grado de NPIQ en T2, mientras que el 82.5% aún persistía en T3. El dolor neuropático afectó al 42% de la población (RR = 1.429; IC del 95% = 1.130-1.806). Las puntuaciones de ansiedad y depresión disminuyeron significativamente en comparación con el valor inicial (reducción de 2.5 puntos HAD, p <0.05). La capacidad funcional de la población no mostró cambios significativos. En T2, la educación se consideró un predictor de síntomas CIPN autoinformados (OR=1.314, IC 95%=1.002-1.723, p=0,048). Conclusión: La baja educación puede comprometer la capacidad del paciente para informar los síntomas de CIPN. Este estudio llama la atención sobre la necesidad de utilizar instrumentos específicos para la detección temprana de CIPN.


Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Peripheral Nervous System Diseases , Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Paclitaxel/therapeutic use , Neurotoxicity Syndromes , Docetaxel/therapeutic use , Oxaliplatin/therapeutic use , Intestinal Neoplasms/drug therapy
8.
Rev. Salusvita (Online) ; 38(4): 987-1000, 2019.
Article in Portuguese | LILACS | ID: biblio-1117694

ABSTRACT

Introdução: O câncer merece destaque entre as doenças que causam transtornos em adultos e crianças, pois continua sendo um diagnóstico dos mais temidos da atualidade. Vincula-se a um estigma de sofrimento, mutilação e morte, envolvendo uma série de ameaças e dificuldades, que afetam não só a criança, mas sua família como um todo, ao longo do processo de diagnóstico e tratamento Objetivo: Comparar os comportamentos de crianças durante a quimioterapia endovenosa antes e após a aplicação do brinquedo terapêutico instrucional (BTI). Materiais e Métodos: Pesquisa não controlada do tipo "antes e depois", realizada na oncopediatria de um hospital público. Foram avaliadas 10 crianças submetidas a quimioterapia endovenosa. Na coleta de dados, utilizou-se um questionário com questões sociodemográficas, clínicas, comportamentais e reações esboçadas durante o tratamento, antes e após a sessão de BTI. A análise de dados foi feita no programa SPSS, sendo realizado o teste de Mc Nemar, considerando um intervalo de confiança de 95%. Resultados: O câncer infantil mais frequente foi a Leucemia Linfoide Aguda (40%). Dos comportamentos analisados, percebeuse redução significativa após o uso do BTI do comportamento "postura retraída". Conclusão: O BTI representou uma ferramenta importante no controle da ansiedade e sofrimento gerado pelo tratamento quimioterápico endovenoso.


Introduction: Cancer plays a notable role among diseases that afflict adults and children. Its diagnosis is still much feared and connects to a stigma of suffering, mutilation and death. It is related to difficulties and treats that affects not only the child but also his whole family during the long process of diagnosis and treatment. Objective: to compare the behaviors of children during intravenous chemotherapy before and after the application of therapeutic instructional toy (BTI). Materials and methods: Uncontrolled search such as "before and after", held in oncopediatria of a public hospital. Ten children were evaluated, subjected to intravenous chemotherapy. For collection, it was used a questionnaire asking for sociodemographic, clinical and behavioral questions, as well as issues and reactions outlined during treatment, before and after the session of BTI. The data analysis was done in SPSS program, being carried out the Mc Nemar test, assuming a confidence interval of 95%. Results: the most frequent childhood cancer was Acute Lymphoblastic leukemia (40%). Among the behaviors examined, it was significantly reduced after the use of BTI "retracted posture" behavior. Conclusion: the BTI represented an important tool in the control of anxiety and suffering generated by intravenous chemotherapy treatment.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Play and Playthings , Child, Hospitalized/psychology , Drug Therapy/psychology , Emotions , Neoplasms/drug therapy , Ovarian Neoplasms/drug therapy , Infusions, Intravenous/psychology , Leukemia, Myeloid, Acute/drug therapy , Punctures/psychology , Child Behavior/psychology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Kidney Neoplasms/drug therapy
9.
Braz. j. med. biol. res ; 52(5): e7992, 2019. graf
Article in English | LILACS | ID: biblio-1001527

ABSTRACT

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.


Subject(s)
Animals , Female , Rabbits , Ovarian Neoplasms/drug therapy , CD4-Positive T-Lymphocytes/drug effects , Apoptosis , Th1 Cells/drug effects , MicroRNAs/metabolism , Artesunate/pharmacology , Ovarian Neoplasms/immunology , CD4-Positive T-Lymphocytes/cytology , Down-Regulation , Cell Differentiation , Th1 Cells/cytology , Flow Cytometry , Artesunate/therapeutic use , Mice, Inbred C57BL , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology
10.
Biol. Res ; 51: 58, 2018. graf
Article in English | LILACS | ID: biblio-1011402

ABSTRACT

BACKGROUND: Studies have demonstrated that transforming growth factor beta-1 (TGF-ß1) exhibits oncogenic activity in different types of cancer, including ovarian cancer (OC). However, its regulatory mechanism in OC and whether TGF-ß1 is involved in chemosensitivity regulation remains unclear. Thus, the aim of this study was to investigate the role of TGF-ß1 in OC. METHODS: The OC cell line SKOV3 was employed, and TGF-ß1 overexpression or knockdown vectors were constructed. The cell proliferation of SKOV3 was evaluated with the cell counting kit (CCK8) kit after treatment with different concentrations of cis-platinum. Western blot and protein immunoprecipitation were employed to detect changes in BRCA1 and Smad3 expression and their interactions. Tumor growth in nude mice was evaluated. RESULTS: The results showed that TGF-ß1 knockdown increased chemosensitivity by promoting BRCA1 expression and Smad3 phosphorylation. In vivo studies showed that TGF-ß1 knockdown significantly inhibited the growth of tumors, also by upregulating BRCA1 expression and Smad3 phosphorylation. CONCLUSION: Taken together, our results suggest that TGF-ß1 knockdown inhibits tumor growth and increases chemosensitivity by promotion of BRCA1/Smad3 signaling.


Subject(s)
Humans , Animals , Male , Female , Ovarian Neoplasms/metabolism , Down-Regulation/physiology , Genes, BRCA1/physiology , Smad3 Protein/physiology , Transforming Growth Factor beta1/physiology , Ovarian Neoplasms/pathology , Ovarian Neoplasms/drug therapy , Immunohistochemistry , Cells, Cultured , Blotting, Western , Drug Resistance, Neoplasm/physiology , Tumor Suppressor Proteins/physiology , Cell Line, Tumor , Cell Proliferation , Smad3 Protein/analysis , Transforming Growth Factor beta1/analysis , Gene Knockdown Techniques , Real-Time Polymerase Chain Reaction , Mice, Inbred BALB C
11.
Yonsei Medical Journal ; : 51-56, 2018.
Article in English | WPRIM | ID: wpr-742505

ABSTRACT

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.


Subject(s)
14-3-3 Proteins/metabolism , Adult , Aged , Cell Line, Tumor , Cisplatin/therapeutic use , Disease-Free Survival , Down-Regulation , Female , Gene Knockdown Techniques , Gene Silencing , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Prognosis , Young Adult
12.
Rev. medica electron ; 39(supl.1): 729-740, 2017.
Article in Spanish | LILACS, CUMED | ID: biblio-902252

ABSTRACT

Introducción: actualmente en Cuba y en todo el mundo, el cáncer de ovario representa la octava causa más importante de neoplasias malignas en la mujer, pero es la cuarta causa relacionada con la mortalidad. Objetivo: identificar el comportamiento por tipos histológicos y por tratamientos del cáncer de ovario. Materiales y métodos: se realizó un estudio descriptivo, retrospectivo, de pacientes con cáncer de ovario, atendidas en el Hospital "Ramón González Coro", La Habana. En el período comprendido entre enero de 2001 a julio de 2013. Las unidades de análisis fueron las historias clínicas de las 98 pacientes que se estudiaron. Resultados: se observó que 69,3 % tenían entre 31 y 60 años de edad. La edad promedio del grupo completo fue 48,2 años, la mitad de las pacientes no refirieron antecedentes patológicos. La paridad promedio fue 1,3. En 3,1 % tenían antecedentes de una neoplasia maligna confirmada y tratada, 14,3 % poseían antecedentes familiares maternos de neoplasia maligna; siendo el motivo de consulta más frecuente el "dolor en bajo vientre" (40,8 %). No hubo asociación significativa entre los estadios (FIGO) y el tipo de cáncer. Conclusiones: los resultados obtenidos se comportan, en general, de acuerdo a patrones epidemiológicos reportados internacionalmente, aunque la frecuencia de cáncer epitelial fue menor que la referida en la literatura consultada. La mayoría de los cánceres estudiados estaban en estadios I y III (AU).


Background: currently in Cuba and around the world, the ovarian cancer represents the eighth most important cause of malignant neoplasia in women, but it is the fourth cause related with mortality. Objective: identifying behavior by histological types and by ovarian cancer treatment. Materials and methods: a descriptive, retrospective study was carried out in patients with ovarian cancer attended in the Hospital "Ramón González Coro", Havana, in the period between January 2001 and July 2013. The analysis units were the clinical records of the 98 studied patients. Outcomes: it was observed that 69.3 % were aged 31-60 years. The average age of the entire group was 48.2 years; half of the patients did not refer pathological antecedents. The average parity was 1.3. 3.1 % had antecedents of confirmed and treated malignant neoplasia; 14.3 % had maternal antecedents of malignant neoplasia, being the most frequent motive of consultation "pain in the low womb" (40.8 %). There was not significant association between the stages (FIGO) and the cancer type. Conclusions: the obtained results behave, in general, according to the epidemiological patterns internationally reported, though the frequency of the epithelial cancer was lower than the one referred in the consulted literature. Most of the studied cancers were in stages I and III (AU).


Subject(s)
Humans , Male , Female , Ovarian Neoplasms/epidemiology , Carcinoma, Ovarian Epithelial/epidemiology , Ovarian Neoplasms/surgery , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Ovarian Neoplasms/prevention & control , Ovarian Neoplasms/drug therapy , Biopsy/methods , Carcinoma, Ovarian Epithelial/diagnosis , Gynecology/methods
13.
Santiago; Chile. Ministerio de Salud; 2017. ilus, tab.
Monography in Spanish | LILACS, BRISA | ID: biblio-882201

ABSTRACT

INTRODUCCIÓN: El cáncer epitelial de ovario es una alteración celular que se origina en el tejido proveniente del epitelio celómico de este órgano, representando al 85% de los tumores ováricos y su incidencia aumenta con la edad, ocurriendo la mitad de los casos en mujeres mayores de 65 años con un promedio de 55 años. Se clasifican en tumores potenciales benignos, de malignidad baja o borderline, y malignos. Este informe evalúa bevacizumab en pacientes con cáncer de ovario epitelial avanzado (primera línea) o recurrente/resistente a platino (segunda línea), y trabectedina para cáncer de ovario epitelial recurrente sensible a platino (segunda línea). TECNOLOGÍAS SANITARIAS ANALIZADAS: Bevacizumab y Trabectedina. EFICACIA DE LOS TRATAMIENTOS: Se utilizaron 14 revisiones sistemáticas, las cuales incluyeron evidencia de efectividad de bevacizumab (5 estudios primarios) y trabectedina (1 estudio primario), en pacientes con cáncer de ovario epitelial avanzado o recurrente. La terapia de bevacizumab más quimioterapia no tiene efecto importante comparado con quimioterapia sola al medir la mortalidad al largo plazo en pacientes con cáncer ovárico epitelial avanzado o recurrente. Esto debido a que el estudio OCEANS reporta que no hay diferencia entre los grupos estudiados y el estudio ICON7 reporta una diferencia mínima que bordea la similitud de ambos brazos del estudio. Bevacizumab más quimioterapia tendría poca o ninguna diferencia comparado con quimioterapia sola, al medir la progresión de la enfermedad a corto y largo plazo en pacientes con cáncer ovárico avanzado o recurrente. En cuanto a la terapia de trabectidina más doxorubicina, ésta probablemente reduce levemente la mortalidad y la progresión de la enfermedad, comparado con la terapia de solo doxorubicina, en pacientes con cáncer de ovario epitelial avanzado o recurrente. ANÁLISIS ECONÓMICO: La mayoría de los estudios de costo efectividad encontrados sugieren que bevacizumab se encuentra dominado o no es costo-efectivo en aquellos países en donde se realizaron evaluaciones económicas. Dos estudios (desde la perspectiva de Medicare y Canadá) mencionan que podría ser costo efectivo. No se encontraron estudios de costo efectividad realizados en América Latina que evalúen el uso bevacizumab para cáncer de ovario avanzado. No se encontraron evaluaciones económicas que hayan evaluado la costo-efectividad de la trabectedina en cáncer ovárico epitelial o endotelial recurrente en países de América Latina. Todas las evaluaciones económicas incluidas corresponden a países de altos ingresos, y presentaron un RCEI (Razón de Costo Efectividad Incremental) superior al umbral publicado por el autor para cada país. Sin embargo las evaluaciones financiadas por el productor de la tecnología consideran que el agregado de trabectedina a doxorubicina vs doxorubicina sola, podría ser costo-efectiva. La mayoría de las políticas de cobertura de América Latina no cubren el bevacizumab para cáncer de ovario avanzado, con excepción de Argentina y México. La mayoría de los financiadores pertenecientes a países de altos ingresos brindan cobertura para para pacientes con cáncer de ovario epitelial, trompa de Falopio (estadíos FIGO, IIIB, IIIC y IV) en combinación con carboplatino, y paclitaxel, o gemcitabina, en primera línea luego de cirugía, o ante la primera recurrencia, en pacientes que presenten buen estado funcional (ECOG 0-2) y una expectativa de vida mayor a un año al momento de iniciar el tratamiento. No se encontraron políticas de cobertura en países de América Latina que incluyan a la trabectedina en cáncer ovárico epitelial o endotelial recurrente resistente. Las políticas de cobertura relevadas pertenecientes a países de altos ingresos no brindan cobertura para la trabectedina en esta condición de salud. El cálculo de impacto presupuestal arroja que bevacizumab, en 2018, para 1ª línea tendría un costo de $MM 13.801, en 2ª línea de $MM 6.370, y trabectedina de $MM 1.815. CONCLUSIÓN: Para dar cumplimiento al artículo 28° del Reglamento que establece el proceso destinado a determinar los diagnósticos y tratamientos de alto costo con Sistema de Protección Financiera, según lo establecido en los artículos 7°y 8° de la ley N°20.850, aprobado por el decreto N°13 del Ministerio de Salud, se concluye que el presente informe de evaluación se considera favorable, de acuerdo a lo establecido en el Título III. de las Evaluaciones Favorables de la Norma Técnica N° 0192 de este mismo ministerio.


Subject(s)
Humans , Bevacizumab/therapeutic use , Ovarian Neoplasms/drug therapy , Health Evaluation/economics , Technology Assessment, Biomedical/economics
14.
Lima; s.n; jun. 2016. tab.
Non-conventional in Spanish | LILACS, BRISA | ID: biblio-847570

ABSTRACT

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar la seguridad y eficacia del uso de bevacizumab en combinación con quimioterapias que no contengan platino en el tratamiento de pacientes con diagnóstico de cáncer de ovario metastásico dentro del sistema de EsSalud, indicación actualmente no contemplada en el Petitorio Farmacológico de ESSALUD. Esta acción sigue lo estipulado en la Directiva N° 002-IETSI-ESSALUD-2015(1) y el objetivo final es determinar la seguridad y eficacia de bevacizumab en combinación con quimioterapias que no contengan platino en el escenario específico descrito a continuación. Generalidades: El cáncer de ovario es uno de los cánceres que con mayor frecuencia afectan a las mujeres en todo el mundo. De hecho, constituye el quinto tipo de cáncer más común en mujeres y la cuarta causa más común de muerte por cáncer en las mismas. De acuerdo con el registro mundial de cáncer, en la actualidad cada año se diagnostican aproximadamente -240 000 nuevos casos de cáncer de ovario se diagnostican en todo el mundo y -150 000 mujeres mueren a consecuencia de esta enfermedad. Esto se debe en gran medida a que, a diferencia de otros tumores sólidos, el cáncer de ovario tiene una fuerte predisposición a diseminarse peritonealmente de manera precoz lo que explica el alto porcentaje de mujeres que al momento de ser diagnosticadas se encuentran ya en estadios avanzados de enfermedad. Tecnología Sanitaria de Interés: Bevacizumab es un anticuerpo monoclonal específico contra el factor de crecimiento del endotelio vascular (VEGF por sus siglas en inglés) humano. Al ligarse al VEGF, específicamente al VEGF-A, actúa como una citoquina antiangiogénica previniendo su interacción con los receptores del VEGF (VEGFR-1 and VEGFR-2), mediando la inhibición del crecimiento y mantenimiento de los vasos sanguíneos de una variedad de células tumorales. METODOLOGÍA: El protocolo de esta revisión sistemática fue preparado y revisado con el equipo técnico de IETSI. Las siguientes fuentes han sido revisadas y consultadas con la intención de buscar la mejor evidencia disponible que directamente responda a la pregunta PICO de esta evaluación: \tAmerican Society of Clinical Oncology (ASCO), \tCanadian Agency for Drugs and Technologies in Health (CADTH), Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, European Association of Urology Guidelines (EAUG), European Society for Medical Oncology (ESMO), Institute for Health Technology Assessment Ludwig Boltzmann Gelsellschaft (LBI-HTA) de Austria, Medline/Pubmed, National Cancer Institute (NCI) de los Estados Unidos, National Comprehensive Cancer Network (NCCN), National Guideline Clearinghouse (NCG) de los Estados Unidos, National Institute for Health and Care Excellence (NICE) del Reino Unido, National Institute for Health Research (NIHR) del Reino Unido, Scopus, Scottish Medicines Consortium (SMC), Translating Research into Practice (TRIP Database), Web of Science. RESULTADOS: En resumen luego de revisar un total de 374 referencias resultados de nuestra búsqueda bibliográfica, logramos filtrar 107 referencias relevantes para nuestra pregunta PICO de interés (Tabla 1), de los cuales sólo 6 referencias fueron finalmente seleccionados para nuestro análisis toda vez que constituían referencias que respondían a la pregunta PICO de interés de este dictamen, incluyendo 2 guías de práctica clínica, 1 evaluación de tecnología y 3 referencias generadas por un ensayo clínico de fase III. CONCLUSIONES: A la fecha, no se dispone de evidencia suficiente para recomendar bevacizumab en combinación con quimioterapia que no contenga platino en comparación con quimioterapia a base de PLD como una alternativa de tratamiento eficaz, segura y costo efectiva para pacientes con cáncer de ovario metastásico resistente a platino. La evidencia disponible sugiere que, comparado con quimioterapia a base de PLD sola, el uso de bevacizumab en combinación con quimioterapia que no contenga platino sólo ofrece un beneficio mínimo (diferencia de medianas de SLP, ­1.9 meses) en términos de sobrevida libre de progresión. La evidencia disponible sugiere que, comparado con quimioterapia a base de PLD sola, el uso de bevacizumab en combinación con quimioterapia que no contenga platino no ofrece mayor beneficio en términos de sobrevida global, tasa de respuesta objetiva o calidad de vida.A la fecha, la evidencia disponible da cuenta de que bevacizumab en combinación con quimioterapia que no contenga platino representa una alternativa de tratamiento con mayor frecuencia de efectos adversos que la quimioterapia que no contenga platino sola. Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) decide no aprobar el uso de bevacizumab en combinación con PLD para el tratamiento de cáncer de ovario metastásico resistente a platino.


Subject(s)
Humans , Bevacizumab/administration & dosage , Neoplasm Metastasis , Ovarian Neoplasms/drug therapy , Platinum , Cost-Benefit Analysis , Drug Therapy, Combination , Peru , Technology Assessment, Biomedical
15.
Article in English | WPRIM | ID: wpr-216440

ABSTRACT

OBJECTIVE: Bevacizumab was recently approved by the US Food and Drug Administration for use in recurrent platinum resistant epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) when no more than two prior cytotoxic regimens have been used; due to concerns for gastrointestinal perforation. We sought to determine bevacizumab-related toxicities in heavily pretreated recurrent EOC. METHODS: We performed a retrospective chart review of patients with recurrent EOC, FTC, and PPC from 2001 to 2011. Patients who received at least two prior chemotherapy regimens before bevacizumab were included. Medical records were reviewed for bevacizumab associated toxicities. The Wilcoxon-Mann-Whitney test was used to compare quantitative variables. Survival was estimated with the Kaplan-Meier method. RESULTS: Sixty patients met inclusion criteria. At the start of bevacizumab treatment, the median age was 60 years and the median body mass index was 26.5 kg/m². More than 50% of patients received bevacizumab after three prior cytotoxic regimens. Grade 3 or higher bevacizumab associated toxicity events occurred in four patients, including one patient who developed a rectovaginal fistula. The median overall survival from the start of bevacizumab treatment was 21.05 months (95% CI, 18.23 to 32.67; range, 1.9 to 110 months). The number of cytotoxic regimens prior to bevacizumab treatment did not differ in those that experienced a toxicity versus those that did not (p=0.66). CONCLUSION: The use of bevacizumab in heavily pretreated EOC, FTC, or PPC is worth consideration.


Subject(s)
Adult , Aged , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/adverse effects , Fallopian Tube Neoplasms/drug therapy , Female , Humans , Intestinal Perforation/chemically induced , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Retrospective Studies
16.
Article in English | WPRIM | ID: wpr-100616

ABSTRACT

OBJECTIVE: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. METHODS: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged < or =40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. RESULTS: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. CONCLUSION: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.


Subject(s)
Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Fertility Preservation , Humans , Laparoscopy , Live Birth , Neoplasm Recurrence, Local/blood , Neoplasm Staging , Neoplasms, Glandular and Epithelial/drug therapy , Organ Sparing Treatments , Ovarian Neoplasms/drug therapy , Pregnancy , Pregnancy Rate , Retrospective Studies , Term Birth , Treatment Outcome , Young Adult
17.
Yonsei Medical Journal ; : 33-40, 2016.
Article in English | WPRIM | ID: wpr-199916

ABSTRACT

PURPOSE: This study aimed to investigate whether Mullerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.


Subject(s)
Anti-Mullerian Hormone/pharmacology , Apoptosis/drug effects , Calcitriol/pharmacology , Caspase 3/metabolism , Caspase 9/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Fragmentation/drug effects , Enzyme-Linked Immunosorbent Assay , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Growth Inhibitors/metabolism , Humans , Ovarian Neoplasms/drug therapy , Receptors, Peptide , Receptors, Transforming Growth Factor beta , Signal Transduction/drug effects
18.
Article in English | WPRIM | ID: wpr-213437

ABSTRACT

Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeutic agents and to be associated with a worse prognosis than the more common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients with ovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well as the efforts to develop novel treatment strategies in the setting of both front-line treatment and salvage treatment for recurrent disease are needed. In this presentation, we first summarize the mechanism responsible for carcinogenesis. Then, we highlight the promising therapeutic targets in ovarian CCC and provide information on the novel agents which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can be best combined with targeted agents in the treatment of ovarian CCC.


Subject(s)
Adenocarcinoma, Clear Cell/drug therapy , Antineoplastic Agents/therapeutic use , Female , Forecasting , Humans , Neoplasm Recurrence, Local/prevention & control , Ovarian Neoplasms/drug therapy
19.
Braz. j. med. biol. res ; 49(12): e5717, 2016. graf
Article in English | LILACS | ID: biblio-828174

ABSTRACT

Propofol is one of the most commonly used intravenous anesthetic agents during cancer resection surgery. A previous study has found that propofol can inhibit invasion and induce apoptosis of ovarian cancer cells. However, the underlying mechanisms are not known. miR-9 has been reported to be little expressed in ovarian cancer cells, which has been related to a poor prognosis in patients with ovarian cancer. Studies have also demonstrated that propofol could induce microRNAs expression and suppress NF-κB activation in some situations. In the present study, we assessed whether propofol inhibits invasion and induces apoptosis of ovarian cancer cells by miR-9/NF-κB signaling. Ovarian cancer ES-2 cells were transfected with anti-miR-9 or p65 cDNA or p65 siRNA for 24 h, after which the cells were treated with different concentrations of propofol (1, 5, and 10 μg/mL) for 24 h. Cell growth and apoptosis were detected using MTT assay and flow cytometry analysis. Cell migration and invasion were detected using Transwell and Wound-healing assay. Western blot and electrophoretic mobility shift assay were used to detect different protein expression and NF-κB activity. Propofol inhibited cell growth and invasion, and induced cell apoptosis in a dose-dependent manner, which was accompanied by miR-9 activation and NF-κB inactivation. Knockdown of miR-9 abrogated propofol-induced NF-κB activation and MMP-9 expression, reversed propofol-induced cell death and invasion of ES-2 cells. Knockdown of p65 inhibited NF-κB activation rescued the miR-9-induced down-regulation of MMP-9. In addition, overexpression of p65 by p65 cDNA transfection increased propofol-induced NF-κB activation and reversed propofol-induced down-regulation of MMP-9. Propofol upregulates miR-9 expression and inhibits NF-κB activation and its downstream MMP-9 expression, leading to the inhibition of cell growth and invasion of ES-2 cells.


Subject(s)
Humans , Female , MicroRNAs/drug effects , Neoplasm Invasiveness/prevention & control , NF-kappa B/drug effects , Ovarian Neoplasms/drug therapy , Propofol/therapeutic use , Protective Agents/therapeutic use , Apoptosis/drug effects , Blotting, Western , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , NF-kappa B/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Polymerase Chain Reaction
20.
Clinics ; 70(5): 339-345, 05/2015. tab
Article in English | LILACS | ID: lil-748275

ABSTRACT

OBJECTIVES: The purpose of this study was to analyze the characteristics of oral-motor movements and facial mimic in patients with head and neck burns. METHODS: An observational descriptive cross-sectional study was conducted with patients who suffered burns to the head and neck and who were referred to the Division of Orofacial Myology of a public hospital for assessment and rehabilitation. Only patients presenting deep partial-thickness and full-thickness burns to areas of the face and neck were included in the study. Patients underwent clinical assessment that involved an oral-motor evaluation, mandibular range of movement assessment, and facial mimic assessment. Patients were divided into two groups: G1 - patients with deep partial-thickness burns; G2 - patients with full-thickness burns. RESULTS: Our final study sample comprised 40 patients: G1 with 19 individuals and G2 with 21 individuals. The overall scores obtained in the clinical assessment of oral-motor organs indicated that patients with both second- and third-degree burns presented deficits related to posture, position and mobility of the oral-motor organs. Considering facial mimic, groups significantly differed when performing voluntary facial movements. Patients also presented limited maximal incisor opening. Deficits were greater for individuals in G2 in all assessments. CONCLUSION: Patients with head and neck burns present significant deficits related to posture, position and mobility of the oral myofunctional structures, including facial movements. .


Subject(s)
Animals , Female , Humans , Mice , /antagonists & inhibitors , Neoplasms, Glandular and Epithelial/complications , Ovarian Neoplasms/complications , Paraneoplastic Syndromes , Thrombocytosis/etiology , Antibodies, Monoclonal/therapeutic use , Blood Platelets/immunology , Disease Models, Animal , Disease-Free Survival , /blood , /immunology , Kaplan-Meier Estimate , Mice, Knockout , Neoplasms, Glandular and Epithelial/blood , Neoplasms, Glandular and Epithelial/drug therapy , Ovarian Neoplasms/blood , Ovarian Neoplasms/drug therapy , Platelet Count , Proportional Hazards Models , /deficiency , Signal Transduction , Thrombopoietin/antagonists & inhibitors , Thrombopoietin/blood
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