Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Oncogene ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705064

RESUMO

Ovarian cancer selective metastasizes to the omentum contributing to the poor prognosis associated with ovarian cancer. However, the mechanism underlining this propensity and therapeutic approaches to counter this process has not been fully elucidated. Here, we show that MCP-1 produced by omental adipocytes binding to its cognate receptor CCR-2 on ovarian cancer cells facilitates migration and omental metastasis by activating the PI3K/AKT/mTOR pathway and its downstream effectors HIF-1α and VEGF-A in cell lines, xenografts, and transgenic murine models. MCP-1 antibody significantly decreased tumor burden and increased survival of mice in vivo. Interestingly, metformin decreased omental metastasis at least partially by inhibiting MCP-1 secretion from adipocytes independent of direct effects on cancer cells. Together this suggests a novel target of MCP-1/CCR-2 axis that could benefit ovarian cancer patients.

2.
Bioorg Chem ; 93: 103315, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605927

RESUMO

Glutamic-oxaloacetic transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements for sustained proliferation. As such, the GOT1 inhibitor may provide a new strategy for the treatment of various cancers. Adapalene has been approved by FDA for the treatment of acne, pimples and pustules, and it may also contribute to the adjunctive therapy for advanced stages of liver and colorectal cancers. In this work, we first examined the enzyme inhibition of over 500 compounds against GOT1 in vitro. As a result, Adapalene effectively inhibited GOT1 enzyme in a non-competitive manner. MST and DARTS assay further confirmed the high affinity between Adapalene and GOT1. Furthermore, the growth and migration of ovarian cancer ES-2 cells were obviously inhibited by the treatment of Adapalene. And it induced the apoptosis of ES-2 cells according to Western blot and Hoechst 33258 straining. In addition, molecular docking demonstrated that Adapalene coordinated in an allosteric site of GOT1 with low binding energy. Furthermore, knockdown of GOT1 in ES-2 cells decreased their anti-proliferative sensitivity to Adapalene. Together, our data strongly suggest Adapalene, as a GOT1 inhibitor, could be regarded as a potential drug candidate for ovarian cancer therapy.

3.
J Cancer ; 10(8): 1902-1908, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205548

RESUMO

Objectives: Understanding the prevalence and characteristics of high-risk human papillomavirus (hrHPV) with the large-scale multicenter data based on a US FDA-approved testing method is important to guide ongoing vaccination programs in China. Methods: We conducted a retrospective observational study based on data from 11 large hospitals in central and eastern China. From October 1st, 2012 to December 31st, 2016, a total of 480,034 cervical specimens were collected, and 414,540 eligible participants (14-80 years, mean age 39.9 years) were included and tested using Cervista High-Risk HPV Assay (Hologic Inc., Bedford, Mass, USA). Results: The overall hrHPV prevalence in this study was 17.8% (73,713/414,540), with Wuhan slightly higher than Zhejiang (18.6% vs. 17.6%, P < 0.001). The prevalence showed a declining trend from 2012 to 2016. The most common hrHPV group was A9 (61.7%), followed by A5/A6 (29.4%) and A7 (25.6%). A U-shaped curve was observed for age-specific hrHPV prevalence: ≤19 years and ≥50 years were higher than other age groups. Conclusion: In pre-vaccination period, A9 was the most dominant hrHPV group, and infections were most likely to occur at younger and older ages. The prevalence of hrHPV varied by cities and age groups, suggesting vaccination programs should be propagated in a population-specific approach.

4.
Gynecol Oncol ; 154(2): 345-353, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31242966

RESUMO

OBJECTIVE: Cervical HR-HPV persistence is the main risk factor for cervical cancer. We aimed to investigate the association of age and viral factors with HR-HPV persistence. METHODS: From 2010 to 2017, 343,128 women underwent 390,411 tests performed by the Cervista HR-HPV assay (Data C3) and 157,123 women underwent 206,505 tests performed by the GenoArray HR-HPV assay (Data G14) in nine medical centers located in central and eastern China. We combined the test results and identified 9234 HPV-specific baseline-negative records for time-to-event analyses. The study endpoint event was defined as clearance of type/group-specific HPV. Therefore, hazard ratio (HR) < 1 indicated a higher risk of HPV persistence, which is contrary to the common meaning of HR. RESULTS: The median persistence time was 375 and 541.5 days for Data C3 and Data G14, respectively. For every 5-year increase in age, a 15% (95% confidence interval [CI], 11%-19%) decrease in the clearance rate was observed only after 400 days of infection. For each additional co-infected HPV, the HR was 1.80 (95% CI, 1.63-1.97) on infection initiation but decreased by 22% (95% CI, 18%-26%) every 100 days. The HR of infection recurrence was 0.48 (95% CI, 0.32-0.72). The findings were consistent across different populations and test methods and were robust in sensitivity analysis. CONCLUSIONS: We found a time-dependent association of age and viral factors with HPV clearance. Older age reduced HPV clearance only after 400 days of infection. Co-infection promoted HPV clearance in the beginning, but the effect attenuated and reversed as infection persisted. Recurrent same-type infection cleared slower than the previous one.


Assuntos
Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Adulto , Fatores Etários , Idoso , Neoplasia Intraepitelial Cervical/virologia , China , Feminino , Seguimentos , Humanos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Neoplasias do Colo do Útero/virologia
5.
J Colloid Interface Sci ; 535: 408-414, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30317081

RESUMO

Herein, we report a novel nanocomposite consisting of n-type Sn-doped hematite and p-type CaMn2O4 nanowire (CaMn2O4/α-Fe2O3). The nanocomposite was characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), ultraviolet-visible absorption spectroscopy, X-ray photoelectron spectroscopy (XPS), which showed that nanospindle-like Sn-doped hematite and CaMn2O4 nanowire contact intimately in the nanocomposite, resulting in efficient charge transfer and separation. Photoelectrochemical results reveal that the nanocomposite possesses higher donor density, enhanced conductivity and lower overpotential for dioxygen evolution. In addition, the nanocomposite demonstrates high photocatalytic activity for water oxidation to produce oxygen in a photoelectrochemical cell. The amount of O2 evolved from the optimized photoanode of the photoelectrochemical cell was 1.98 µmol in 2 h of simulated sunlight irradiation. This work demonstrates a facile synthesis of a novel nanocomposite as anode material for photocatalytic water oxidation to produce O2.

6.
Int J Gynecol Cancer ; 28(7): 1410-1417, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30142125

RESUMO

OBJECTIVE: Although most gestational trophoblastic neoplasias (GTN) are sensitive to chemotherapy, the treatment strategy of patients who achieve normal ß-human chorionic gonadotropin (ß-hCG) after the completion of treatment but with residual lung lesions is undefined, let alone whether residual lung lesions threaten GTN patients with acceptable recurrent risk factors. METHODS: We observed 73 patients with stage III and stage IV GTN treated at the Department of Obstetrics and Gynecology, Tongji Hospital between September 2007 and August 2016. Among these patients, 46 women confirmed to have residual lung lesions with normalized ß-hCG titer levels at 6 weeks after the completion of treatment, and the other 27 were without residual lung lesions. Statistical analysis was used to compare the progression-free survival of these 73 patients. RESULTS: The follow-up period of all 73 patients ranged from 6 to 115 months. Six women relapsed with GTN. There were no significant statistical differences (P > 0.05) between the progression-free survival of the patients with residual lung lesions and those without, even in the subgroup of patients with GTN with recurrent risk factors. CONCLUSIONS: After the achievement of normalized ß-hCG by sufficient chemotherapy, residual lung lesions do not alter the prognosis of patients with GTN, even if the patients are with other recurrent risk factors.


Assuntos
Doença Trofoblástica Gestacional/patologia , Neoplasias Pulmonares/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Doença Trofoblástica Gestacional/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Gravidez , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Oncol Lett ; 16(1): 793-800, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29963147

RESUMO

Despite an improvement in the efficacy of chemotherapeutic agents, the outcome of patients with prostate cancer remains poor. MicroRNA (miRNA/miR)-139 expression is often downregulated in multiple types of tumor, including in prostate cancer. The aim of the present study was to investigate the inhibitory effect of miR-139 on the PC-3, C4-2B and LNCaP prostate cancer cell lines. Analysis of the cell cycle of PC-3, C4-2B and LNCaP cells transfected with miR-139 revealed a significantly increased percentage of cells in the G1 phase and a decreased percentage in the S and G2 phases compared with those transfected with a negative control miRNA. The growth inhibitory rate of miR-139-transfected cells 24, 48 and 72 h after transfection were 32.83±2.61, 52.58±3.2 and 62.36±4.55% in PC-3 cells; 30.28±2.25, 51.74±3.27 and 60.80±3.58% in C4-2B cells; and 33.20±2.67, 51.83±3.59 and 61.79±4.85% in LNCaP cells, respectively. The present study revealed that miR-139 inhibited the proliferation of prostate cancer cells by interfering with the cell cycle. Further study into the mechanism by which this happened suggested that miR-139 reduced cyclin D1 expression and inhibited cell proliferation through targeting Notch1.

8.
J Colloid Interface Sci ; 516: 145-152, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29367065

RESUMO

Described herein is the synthesis, characterization and photoelectrochemical behavior of a novel composite consisting of nanolayered manganese-calcium oxide (MCO) and mesoporous tungsten trioxide (WO3). The samples were characterized by transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results demonstrated that superior interfacial contacts had been formed between WO3 and MCO. UV-vis diffuse reflectance spectroscopy (DRS), photoelectrochemical characterization, and incident photon-to-current efficiency (IPCE) revealed an enhanced light harvesting and effective electron-hole separation. A photoelectrochemical (PEC) cell composed of the n-type MCO/WO3 as a photoanode and platinum sheet as a counter electrode was assembled to estimate the feasibility for overall water splitting under a solar simulator illumination. The photocatalytic hydrogen and oxygen production from the photochemical cell with optimized photocatalyst (MCO/WO3-9) under 2 h simulated solar light irradiation was 1.9 µmol and 0.7 µmol, respectively, at low extra bias (0.90 V vs. RHE). Our investigation suggests that coupling MCO with n-type semiconductor WO3 as photoanode is a promising method to improve the activity of overall water splitting to generate oxygen and hydrogen.

9.
Front Med ; 12(5): 509-517, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29218679

RESUMO

This study was performed to evaluate the oncological and reproductive outcomes of childbearing-age women treated with fertility-sparing surgery (FSS) for non-epithelial ovarian tumors in China. One hundred and forty eight non-epithelial ovarian tumor women treated with FSS between January 1, 2000 and August 31, 2015 from two medical centers in China were identified. Progression-free survival (PFS) was 88.5%, whereas overall survival (OS) was 93.9%. Univariate analysis suggested that delivery after treatment is related to PFS (P = 0.023), whereas histology significantly influenced OS. Cox regression analysis suggested that only histology was associated with PFS and OS (P < 0.05). Among the 129 women who completed adjuvant chemotherapy (ACT), none developed amenorrhea. Among the 44 women who desired pregnancy, 35 (79.5%) successfully had 51 gestations including 35 live births without birth defects. Non-epithelial ovarian tumors can achieve fulfilling prognosis after FSS and chemotherapy. Histology might be the only independent prognostic factor for PFS and OS. FSS followed by ACT appeared to have little or no effect on fertility. Meanwhile, postoperative pregnancy did not increase the PFS or OS. Use of gonadotropin-releasing hormone agonist was not beneficial for fertility.


Assuntos
Infertilidade Feminina/prevenção & controle , Tratamentos com Preservação do Órgão , Neoplasias Ovarianas/cirurgia , Taxa de Gravidez , Adolescente , Adulto , Quimioterapia Adjuvante/efeitos adversos , Criança , China , Feminino , Humanos , Infertilidade Feminina/etiologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Gravidez , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
10.
Front Med ; 11(4): 563-569, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28744794

RESUMO

The superiority of the cumulative outcomes of day 5/6 embryo transfer to those of day 2/3 embryo transfer in infertile couples has been debated. This retrospective study included data collected from 1051 patients from July 2011 to June 2014. Multiple maternal baseline covariates were subjected to propensity score matching analysis, and each day 5/6 group woman was matched to one day 2/3 group woman. A systematic meta-analysis was conducted to validate the results. After matching was completed, 217 patients on the day 2/3 group were matched with those on the day 5/6 group, and no significant differences in the baseline characteristics were observed between the two groups. The cumulative pregnancy rate (57.14% vs. 53.46%, OR 1.16, 95% CI 0.79-1.70) and cumulative live birth rate (53.00% vs. 49.77%, OR 1.14, 95% CI 0.78-1.66) of day 5/6 embryo transfers were higher than those of day 2/3 embryo transfers, but this difference was not significant. The mean cycles per live birth and mean days per live birth in the day 5/6 group were significantly lower than those in the day 2/3 group. This study demonstrated that day 5/6 embryo transfer is a more cost-effective and time-efficient policy than day 2/3 embryo transfer to produce a live baby.


Assuntos
Transferência Embrionária , Fertilização In Vitro , Infertilidade , Nascimento Vivo/epidemiologia , Taxa de Gravidez , Adulto , China/epidemiologia , Fase de Clivagem do Zigoto/transplante , Estudos de Coortes , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Feminino , Fertilização In Vitro/métodos , Fertilização In Vitro/estatística & dados numéricos , Humanos , Infertilidade/epidemiologia , Infertilidade/terapia , Masculino , Gravidez , Resultado da Gravidez/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos
11.
Oncol Lett ; 13(6): 4619-4626, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28588720

RESUMO

Although a combination of platinum- and taxane-based chemotherapy is recommended for at least 70% patients with ovarian cancer as treatment subsequent to surgery, the initial response to the chemotherapy is not durable and tumors become resistant. Histone deacetylase and proteasome inhibitors are novel therapeutic agents. However, the moderate antitumoral effect of the inhibitors has restricted their clinical use when used as single agents. The aim of the present study was to investigate the synergistic activity of trichostatin A (TSA) and PS-341 in ovarian cancer cells, along with the investigation of the molecular mechanisms of taxane resistance. The taxane-sensitive ovarian cancer A2780 cell line and its resistant variant, A2780T, were treated with taxane, TSA and PS-341 at various concentrations. An Annexin V assay was performed to determine the levels of cell viability and apoptosis, while flow cytometry and immunofluorescence staining for the mitotic phase-specific protein phosphorylated-histone H3 (Ser10) were used for cell cycle detection. The effects of combined TSA and PS-341 on cell cycle-associated proteins were tested by western blot analysis. Furthermore, the present study examined the apoptosis and cell cycle arrest induced by the 3 agents subsequent to overexpression or downregulation of cyclin B1 in A2780 and A2780T cells, respectively. It was found that TSA interacted synergistically with PS-341, resulting in a marked increase in apoptosis and the rate of G2/M arrest in A2780T cells. A lower basal level of cyclin B1 expression and the incompetence of the upregulation of the cyclin may explain the taxane resistance found in A2780T cells. Collectively, the combination of TSA and PS-341 increased cyclin B1 expression level regardless of the basal expression level, resulting in the proliferation inhibition and apoptosis in A2780 and A2780T cells, which raised the possibility that a combination of the two drugs may represent a novel strategy for the treatment of ovarian cancer, particularly in taxane-resistant ovarian cancer.

12.
Oncotarget ; 8(26): 42983-42996, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28562334

RESUMO

Serous ovarian cancer (SOC) is the most lethal gynecological cancer. Clinical studies have revealed an association between tumor stage and grade and clinical prognosis. Identification of meaningful clusters of co-expressed genes or representative biomarkers related to stage or grade may help to reveal mechanisms of tumorigenesis and cancer development, and aid in predicting SOC patient prognosis. We therefore performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on three public microarray datasets (GSE26193, GSE9891, and TCGA), which included 788 samples and 10402 genes. We detected four modules related to one or more clinical features significantly shared across all modeling datasets, and identified one stage-associated module and one grade-associated module. Our analysis showed that MMP2, COL3A1, COL1A2, FBN1, COL5A1, COL5A2, and AEBP1 are top hub genes related to stage, while CDK1, BUB1, BUB1B, BIRC5, AURKB, CENPA, and CDC20 are top hub genes related to grade. Gene and pathway enrichment analyses of the regulatory networks involving hub genes suggest that extracellular matrix interactions and mitotic signaling pathways are crucial determinants of tumor stage and grade. The relationships between gene expression modules and tumor stage or grade were validated in five independent datasets. These results could potentially be developed into a more objective scoring system to improve prediction of SOC outcomes.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Biologia Computacional , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Estudos de Associação Genética , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Característica Quantitativa Herdável , Reprodutibilidade dos Testes
13.
Front Med ; 11(2): 214-222, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28470508

RESUMO

MicroRNAs (miRNAs) play critical roles in the development and progression in various cancers. Dysfunctional miR-9 expression remains ambiguous, and no consensus on the metastatic progression of ovarian cancer has been reached. In this study, results from the bioinformatics analysis show that the 3'-UTR of the E-cadherin mRNA was directly regulated by miR-9. Luciferase reporter assay results confirmed that miR-9 could directly target this 3'-UTR. miR-9 and E-cadherin expression in ovarian cancer tissue was quantified by qRT-PCR. Migration and invasion were detected by wound healing and Transwell system assay in SKOV3 and A2780. qRT-PCR and Western blot were performed to detect the epithelial‒mesenchymal transition-associated mRNA and proteins. Immunofluorescence technique was used to analyze the expression and subcellular localization of E-cadherin, N-cadherin, and vimentin. The results showed that miR-9 was frequently upregulated in metastatic serous ovarian cancer tissue compared with paired primary ones. Upregulation of miR-9 could downregulate the expression of E-cadherin but upregulate the expression of mesenchymal markers (N-cadherin and vimentin). Overexpression of miR-9 could promote the cell migration and invasion in ovarian cancer, and these processes could be effectively inhibited via miR-9 inhibitor. Thus, our study demonstrates that miR-9 may promote ovarian cancer metastasis via targeting E-cadherin and a novel potential therapeutic approach to control metastasis of ovarian cancer.


Assuntos
Caderinas/metabolismo , MicroRNAs/metabolismo , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Regiões 3' não Traduzidas/genética , Antígenos CD , Caderinas/genética , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , RNA Mensageiro/genética , Vimentina/metabolismo
14.
Oncotarget ; 7(52): 87449-87461, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27974683

RESUMO

Even though infection with human papillomaviruses (HPV) is very important, it is not the sole cause of cervical cancer. Because it is known that genetic variations that result from HPV infection are probably the most important causes of cervical cancer, we used human whole genome array comparative genomic hybridization to detect the copy number variations of genes in cervical squamous cell carcinoma. The results of the array were validated by PCR, FISH and immunohistochemistry. We find that the copy number and protein expression of claudin-1 (CLDN1) increase with the progression of cervical cancer. The strong positive staining of CLDN1 in the cervical lymph node metastasis group received a significantly higher score than the staining in the group with no lymph node metastasis of cervical cancer tissues. The overexpression of CLDN1 in SiHa cells can increase anti-apoptosis ability and promote invasive ability of these cells accompanied by a decrease in expression of the epithelial marker E-cadherin as well as an increase in the expression of the mesenchymal marker vimentin. CLDN1 induces the epithelial-mesenchymal transition (EMT) through its interaction with SNAI1. Furthermore, we demonstrate that CLDN1 overexpression has significant effects on the growth and metastasis of xenografted tumors in athymic mice. These data suggest that CLDN1 promotes invasion and metastasis in cervical cancer cells via the expression of EMT/invasion-related genes. Therefore, CLDN1 could be a potential therapeutic target for the treatment of cervical cancer.


Assuntos
Claudina-1/fisiologia , Neoplasias do Colo do Útero/patologia , Animais , Apoptose , Linhagem Celular Tumoral , Claudina-1/análise , Claudina-1/genética , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Transição Epitelial-Mesenquimal , Feminino , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Invasividade Neoplásica , Neoplasias do Colo do Útero/genética
15.
Oncotarget ; 7(45): 72672-72684, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27682871

RESUMO

OBJECTIVE: The role of Dicer in the prognosis of cancer patients remains controversial. This systematic review is attempted to assess the influence of Dicer as a prognostic predictor for survival in diverse types of cancers. METHODS: Studies were selected as candidates if they published an independent evaluation of Dicer expression level together with the correlation with prognosis in cancers. Random-effect model was applied in this meta-analysis. Heterogeneity between studies was assessed by Q-statistic with P < 0.10 to be statistically significant. Publication bias was investigated using funnel plot and test with Begg's and Egger's test. P < 0.05 was regarded as statistically significant. RESULTS: 24 of 44 articles revealed low Dicer status as a predictor of poor prognosis. The aggregate result of overall survival (OS) indicated that low Dicer expression level resulted in poor clinical outcomes, and subgroup of IHC and RT-PCR method both revealed the same result. Overall analysis of progression-free survival (PFS) showed the same result as OS, and both the two subgroups divided by laboratory method revealed positive results. Subgroup analysis by tumor types showed low dicer levels were associated with poor prognosis in ovarian cancer (HR = 1.93, 95% CI: 1.19-3.15), otorhinolaryngological tumors (HR = 2.39, 95% CI: 1.70-3.36), hematological malignancies (HR = 2.45, 95% CI: 1.69-3.56) and neuroblastoma (HR = 4.03, 95% CI: 1.91-8.50). CONCLUSION: Low Dicer status was associated with poor prognosis in ovarian cancer, otorhinolaryngological tumors and ematological malignancies. More homogeneous studies with high quality are needed to further confirm our conclusion and make Dicer a useful parameter in clinical application.


Assuntos
Biomarcadores Tumorais , RNA Helicases DEAD-box/genética , Neoplasias/genética , Neoplasias/mortalidade , Ribonuclease III/genética , Expressão Gênica , Humanos , Neoplasias/diagnóstico , Prognóstico , Modelos de Riscos Proporcionais , Viés de Publicação
16.
Oncotarget ; 7(32): 52317-52328, 2016 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-27419626

RESUMO

We used oxidative isotope-coded affinity tags (OxICAT) to investigate the global redox status of proteins in human papillomavirus (HPV)-related cervical cancer cells, in order to identify a potential target for gene therapy. Voltage-dependent anion channel 1 (VDAC1) was found to be highly oxidized in HPV-positive cervical cancer cells. VDAC1 expression correlated significantly with the invasion of cervical cancer, the grade of cervical intraepithelial neoplasia (CIN) and the expression of HPV16 E7 in CIN. Knockdown of VDAC1 in cell lines increased the rate of apoptosis, while overexpression of the VDAC1 (respectively) partly reversed the effect. Thus, VDAC1 may promote the malignant progression of HPV-related disease, and treatments designed to suppress VDAC1 could prevent the progression of HPV-induced cervical disease.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias do Colo do Útero/patologia , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Carcinógenos/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Feminino , Humanos , Oxirredução , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/complicações , Proteômica/métodos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
17.
Am J Obstet Gynecol ; 215(4): 460.e1-460.e13, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27133009

RESUMO

BACKGROUND: The safety of ovarian preservation remains uncertain in women with cervical adenocarcinoma and significant risk factors for ovarian metastases vary among different studies. OBJECTIVE: We sought to evaluate the impact of ovarian preservation on prognosis in women with cervical adenocarcinoma and to assess clinical factors associated with ovarian metastases. STUDY DESIGN: A retrospective study of 194 women with cervical adenocarcinoma was conducted and 159 women were followed up until the end of the study. To compare the impact of ovarian preservation on prognosis, women with successful follow-up were studied, including 33 women with ovarian preservation and 126 women who underwent bilateral salpingo-oophorectomy. For women who underwent radical hysterectomy, pelvic lymphadenectomy, and bilateral salpingo-oophorectomy, the risk factors for ovarian metastases were identified. A meta-analysis of the literature was carried out to further validate the findings. RESULTS: There was no significant difference in survival between women with bilateral salpingo-oophorectomy and ovarian preservation (P = .423 for disease-free survival; P = .330 for overall survival). Tumor size (>4 cm), deep cervical stromal invasion, and lymph node metastasis were significant independent prognostic factors related to poor disease-free survival, and lymph node metastasis was significantly associated with overall survival. Of 153 women with cervical adenocarcinoma who underwent bilateral salpingo-oophorectomy, a significant difference was found in the relationship between ovarian metastasis and deep cervical stromal invasion, lymph node metastasis, and parametrial invasion. The meta-analysis showed that clinical stage IIB vs I-IIA (odds ratio, 4.64; 95% confidence interval, 2.11-10.23), deep stromal invasion (odds ratio, 10.63; 95% confidence interval, 3.12-36.02), lymph node metastasis (odds ratio, 8.54; 95% confidence interval, 4.15-17.57), corpus uteri invasion (odds ratio, 7.39; 95% confidence interval, 3.69-14.78), and parametrial invasion (odds ratio, 9.72; 95% confidence interval, 4.67-20.22) were significantly related to ovarian metastasis. CONCLUSION: Ovarian preservation has no effect on prognosis in women with early-stage cervical adenocarcinoma. Risk factors for ovarian metastases were stage IIB, deep cervical stromal invasion, lymph node metastasis, corpus uteri invasion, and parametrial invasion. In women with early-stage cervical adenocarcinoma without these risk factors, ovarian conservation can be considered.


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Neoplasias Ovarianas/secundário , Ovário/cirurgia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Tratamentos com Preservação do Órgão , Ovariectomia , Estudos Retrospectivos , Salpingectomia , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
18.
Oncol Res ; 23(3): 119-28, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26931434

RESUMO

Drug resistance is the leading cause of chemotherapy failure in the treatment of ovarian cancer. So far, little is known about the mechanism of chemoresistance in ovarian cancer. In this study, we explored the mechanism that HSP27 was involved in cisplatin resistance of ovarian cancer both in vitro and clinically. HSP27 protein was found to be upregulated and expressed in cisplatin-resistant ovarian cancer cell line C13*, and HSP27 siRNA transfection reversed the chemoresistance of C13*. We found that HSP27 exerted its chemoresistant role by inhibiting p21 transferring from the nucleus to the plasma through the activation of phosphorylated-Akt pathway. These findings have implications for clinical trials aimed at a potential therapeutic target for ovarian tumors that are refractory to conventional treatment.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Choque Térmico HSP27/genética , Neoplasias Ovarianas/tratamento farmacológico , Quinases Ativadas por p21/biossíntese , Apoptose/efeitos dos fármacos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Cisplatino/administração & dosagem , Citoplasma/genética , Citoplasma/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP27/antagonistas & inibidores , Proteínas de Choque Térmico HSP27/biossíntese , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/genética , Quinases Ativadas por p21/genética
19.
Oncotarget ; 7(15): 21054-63, 2016 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-27014971

RESUMO

BACKGROUND: Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). METHODS: Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). RESULTS: In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. CONCLUSIONS: Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy.


Assuntos
Histerectomia , Excisão de Linfonodo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
20.
Nat Genet ; 47(2): 158-63, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25581428

RESUMO

Human papillomavirus (HPV) integration is a key genetic event in cervical carcinogenesis. By conducting whole-genome sequencing and high-throughput viral integration detection, we identified 3,667 HPV integration breakpoints in 26 cervical intraepithelial neoplasias, 104 cervical carcinomas and five cell lines. Beyond recalculating frequencies for the previously reported frequent integration sites POU5F1B (9.7%), FHIT (8.7%), KLF12 (7.8%), KLF5 (6.8%), LRP1B (5.8%) and LEPREL1 (4.9%), we discovered new hot spots HMGA2 (7.8%), DLG2 (4.9%) and SEMA3D (4.9%). Protein expression from FHIT and LRP1B was downregulated when HPV integrated in their introns. Protein expression from MYC and HMGA2 was elevated when HPV integrated into flanking regions. Moreover, microhomologous sequence between the human and HPV genomes was significantly enriched near integration breakpoints, indicating that fusion between viral and human DNA may have occurred by microhomology-mediated DNA repair pathways. Our data provide insights into HPV integration-driven cervical carcinogenesis.


Assuntos
Alphapapillomavirus/fisiologia , Neoplasia Intraepitelial Cervical/genética , Regulação Neoplásica da Expressão Gênica , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genética , Integração Viral , Adulto , Alphapapillomavirus/genética , Alphapapillomavirus/isolamento & purificação , Sequência de Bases , Linhagem Celular Tumoral , Neoplasia Intraepitelial Cervical/virologia , DNA Viral/genética , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Genoma Humano/genética , Genoma Viral/genética , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Infecções por Papillomavirus/virologia , Análise de Sequência de DNA , Regulação para Cima , Neoplasias do Colo do Útero/virologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA