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1.
Opt Express ; 31(14): 23325-23349, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37475419

RESUMO

A neural network (NN) computational spectrometer has high reconstruction accuracy and a fast operation speed; however, this type of spectrometer also occupies a large amount of storage in an embedded system due to the excessive computation volume. Contrarily, conventional algorithms such as gradient projection for sparse reconstruction (GPSR) take up less storage, but their spectral reconstruction accuracy is much lower than that of an NN. The major reason is that the performance of a GPSR depends greatly on the non-correlation property of optical filters which may pose challenges for optical filters design and fabrication. In this study, a GPSR algorithm, known as NN-GPSR, is applied to achieve high-precision spectral reconstruction enabled by NN-learned highly correlated filters. A group of NN-learned filters shows high-correlation work as the encoder, and an optimized GPSR algorithm works as the decoder. In this case, large computation volume is exempt and prior knowledge of tens of thousands of images are exploited to get appropriate optical filters design. The experiment data indicate that the NN-GPSR performs well in the reconstructing spectrum and requires far less storage.

2.
Opt Express ; 30(13): 23463-23474, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-36225025

RESUMO

The modulation of structural color through various methods has attracted considerable attention. Herein, a new modulation method for the structural colors in all-dielectric photonic crystals (PCs) using energetic ion beams is proposed. One type of periodic PC and two different defective PCs were experimentally investigated. Under carbon-ion irradiation, the color variation primarily originated from the blue shift of the optical spectra. The varying degrees of both the reflection and transmission structural colors mainly depended on the carbon-ion fluences. Such nanostructures are promising for tunable color filters and double-sided chromatic displays based on PCs.

3.
Opt Express ; 29(20): 31915-31923, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615273

RESUMO

We theoretically and experimentally investigate the angle-dependent omnidirectional photonic bandgap (PBG) in one-dimensional photonic crystals (PCs) comprising hyperbolic metamaterials (HMMs) for TM polarization, which is different from blue-shifted PBG in conventional all-dielectric photonic crystals. The frequency range of PBG increases when the incident angles increase, owing to the red-shift and blue-shift of the long-wavelength and short-wavelength band edges, respectively. The red-shifted band edge originates from the phase-variation compensation mechanism between the HMMs and dielectric material. The experimental values are in good agreement with the simulation results. These nanostructures are ideal for fabricating photonic devices such as omnidirectional reflectors.

4.
J Cell Physiol ; 234(3): 2943-2953, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30146796

RESUMO

Cancer-associated fibroblasts (CAFs) play crucial roles in tumor progression, given the dependence of cancer cells on stromal support. Therefore, understanding how CAFs communicate with endometrial cancer cell in tumor environment is important for endometrial cancer therapy. Exosomes, which contain proteins and noncoding RNA, are identified as an important mediator of cell-cell communication. However, the function of exosomes in endometrial cancer metastasis remains poorly understood. In the current study we found that CAF-derived exosomes significantly promoted endometrial cancer cell invasion comparing to those from normal fibroblasts (NFs). We identified a significant decrease of miR-148b in CAFs and CAFs-derived exosomes. By exogenously transfect microRNAs, we demonstrated that miR-148b could be transferred from CAFs to endometrial cancer cell through exosomes. In vitro and in vivo studies further revealed that miR-148b functioned as a tumor suppressor by directly binding to its downstream target gene, DNMT1 to suppress endometrial cancer metastasis. In endometrial cancer DNMT1 presented a potential role in enhancing cancer cell metastasis by inducing epithelial-mesenchymal transition (EMT). Therefore, downregulated miR-148b induced EMT of endometrial cancer cell as a result of relieving the suppression of DNMT1. Taken together, these results suggest that CAFs-mediated endometrial cancer progression is partially related to the loss of miR-148b in the exosomes of CAFs and promoting the transfer of stromal cell-derived miR-148b might be a potential treatment to prevent endometrial cancer progression.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Neoplasias do Endométrio/genética , MicroRNAs/genética , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Neoplasias do Endométrio/patologia , Transição Epitelial-Mesenquimal/genética , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Transdução de Sinais/genética
5.
Opt Express ; 27(4): 5326-5336, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30876132

RESUMO

We theoretically and experimentally investigate the wide-angle perfect absorptance in a photonic heterostructure composed of a metal film and a truncated photonic crystal (PC) with layered hyperbolic metamaterials (HMMs) in the near ultraviolet and visible regions. The wide-angle perfect optical absorption depends on the dispersionless Tamm plasmon polarition (TPP) under TM polarization, which originates from reflection phase compensation condition between the metal and the truncated PC with HMMs. Our experimental results show nearly perfect absorptance over 0.91 in an angle range of 0-45 degree, which facilitates the design of perfect optical absorbers working in a wide angle range.

6.
Opt Express ; 25(12): 13271-13277, 2017 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-28788862

RESUMO

We experimentally investigated near-perfect optical absorption in sandwich structures comprising a thin metallic film whose thickness is larger than the skin depth, a top dielectric layer and a truncated photonic crystal. Single and multiple near-perfect absorptions were realized by tuning the thickness of the top layer. Based on the electromagnetic field intensity distributions at the absorption wavelengths, single near-perfect absorption originated from the tunneling effect of the optical Tamm state, while multiple near-complete absorptions mainly originated from Fabry-Perot resonances. Additionally, the structures showed good one-way absorption properties. The experimental results agreed well with theoretical values. These structures may be important for the fabrication of single or multichannel perfect absorbers.

7.
Opt Express ; 25(24): 30754-30763, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29221101

RESUMO

Enhanced interactions of light with graphene on the surface of a lossless dielectric magnetic mirror (DMM) are studied theoretically and experimentally in the visible range, where the DMM is composed of truncated dielectric photonic crystals (PCs). The absorption of graphene on the DMM was enhanced by about 4-fold for the spectral range within the forbidden gap of PCs over a wide range of incidence angles for both transverse electric and transverse magnetic polarizations compared with that of free-standing graphene. Moreover, the enhanced local electric field on the DMM surface led to much better detection efficiencies of the photocurrent, Raman spectroscopy and enhanced third-harmonic generation of graphene. These results offer a new way to achieve an enhanced interaction of light with graphene and develop new compact graphene-based devices.

8.
J Obstet Gynaecol Res ; 43(3): 564-570, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28127836

RESUMO

AIM: The aim of this study was to assay the clinical characteristics of persistent ectopic pregnancy (PEP) and its influence on ongoing pregnancy. METHODS: We retrospectively reviewed 2498 patients who received salpingostomies as primary management for ectopic pregnancies from January 2004 to December 2009, using medical records and telephone inquiries. Clinical characteristics of the 52 patients (2.08%) who were diagnosed with PEP after salpingostomy were compared with those who received satisfactory treatment. The odds ratios and 95% confidential intervals were calculated for each variable by univariate and (for significantly different factors) multivariate analysis. RESULTS: Preoperatively, patients with PEP after salpingostomy significantly differed from the non-PEP patients in gestational age, mass size and pelvic adhesiolysis. Serum ß-human chorionic gonadotropin levels in PEP patients were monitored after surgery, which had declined by 28.31% on postoperative day (POD) 4, 40.22% on POD 7, 51.46% on POD 10 and 53.43% on POD 21. Repeat ectopic pregnancy (REP) tended to occur more frequently in PEP patients (PEP: 5 cases, 10.20%; non-PEP: 4 cases, 2.80%; P = 0.034). Multivariate analysis showed that pelvic adhesions and PEP were the strongest independent predictors of REP. CONCLUSION: Gestational age, mass size and pelvic adhesions were significantly correlated with PEP. PEP was an independent prognostic factor for REP. However, a multicenter study is needed to support and extend our findings.


Assuntos
Gravidez Ectópica/diagnóstico , Gravidez Ectópica/cirurgia , Salpingostomia , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Idade Gestacional , Humanos , Pelve/patologia , Gravidez , Gravidez Ectópica/sangue , Estudos Retrospectivos , Aderências Teciduais , Resultado do Tratamento , Adulto Jovem
9.
Opt Express ; 22(18): 21403-10, 2014 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-25321518

RESUMO

In this paper, we propose a phase-sensitive Bloch surface wave sensor based on the variable angle spectroscopic ellipsometry and numerically simulate the phase behavior of the sensor. The simulation results show that the dependence of resonant phase is step-like when BSWs are excited. In contrast to the reflectance behavior, even though losses of the dielectric layers are very small, the resonance dip in the reflectivity will be shallow while the step-like change of the reflection phase of the BSW still be remarkable. This means that phase detection is an alternative to reflectivity intensity detection for the sensing applications of the BSWs in this case. Our experimental results indicate that phase detection for the BSW sensors has the potential to achieve the higher sensitivity and the lower limit of detection.

10.
Opt Lett ; 38(6): 959-61, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23503273

RESUMO

We theoretically investigate efficient third-harmonic generation (THG) in the heterostructure with a one-dimensional photonic crystal (PC) and a thick metal film. There are both the fundamental Tamm plasmon mode and the high-order mode in the heterostructure. Commonly these two Tamm plasmon modes just satisfy single-resonance condition, but the double-resonance condition can be fulfilled by using a binary PC in the heterostructure. Taking advantage of the tunneling effect of Tamm plasmon modes, THG in the single-resonance heterostructure is enhanced over 3 orders of magnitude more than that in the single metal film, and that in the double-resonance one is further enhanced nearly 2 orders of magnitude.

11.
Biochem Biophys Res Commun ; 420(2): 343-9, 2012 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-22425989

RESUMO

The selective ER modulator tamoxifen (TAM(1)) is the most widely used ER antagonist for treatment of women with hormone-dependent breast tumor. However, long-term treatment is associated with an increased risk of endometrial cancer. The aim of the present study was to demonstrate new insight into the role of G-protein coupled receptor 30 (GPR30) in the activity of TAM, which promoted endometrial cancer. In endometrial cancer cell lines ISHIKAWA and KLE, the potential of 4-hydroxytamoxifen (OHT), the active metabolite of TAM, 17ß-estradiol (E2) and G1, a non-steroidal GPR30-specific agonist to promote cell proliferation and invasion was evaluated. All agents above induced high proliferative and invasive effects, while the down-regulation of GPR30 or the interruption of MAPK signal pathway partly or completely prevented the action of the regent. Moreover, the RNA and protein expression of GPR30 was up-regulated by G1, E2 or OHT in both cell lines. The present study provided a new insight into the mechanism involved in the agonistic activity exerted by TAM in the uterus.


Assuntos
Neoplasias do Endométrio/induzido quimicamente , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Moduladores Seletivos de Receptor Estrogênico/efeitos adversos , Tamoxifeno/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Invasividade Neoplásica , Tamoxifeno/efeitos adversos , Regulação para Cima
12.
Chin Med J (Engl) ; 133(3): 285-291, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31929361

RESUMO

BACKGROUND: The incidence of uterine cesarean scar defect (niche) is high, and some patients require surgery. Single-port laparoscopy can reduce post-operative pain, and provide better cosmetic effects. This study was performed to evaluate the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scar defect (niche) in women after cesarean section. METHODS: This study included 74 patients who were diagnosed with uterine cesarean niche at the Shanghai First Maternity and Infant Hospital from January 2013 to June 2015. Thirty-seven patients underwent single-port laparoscopy-assisted vaginal surgery as the case group, and the remaining patients underwent vaginal repair surgery as the control group. We collected data from the inpatient and follow-up medical records. The clinical characteristics of these two groups were compared. The odds ratios and 95% confidential intervals were calculated for each variable by univariate and multivariate analyses. RESULTS: Patients who underwent single-port laparoscopy-assisted vaginal repair had a significantly longer operation time (2.3 [2.0-2.7] vs. 2.0 [1.6-2.3] h, P = 0.015), shorter gas passage time (1.2 [1.0-1.5] vs. 1.7 [1.0-2.0] days, P = 0.012), shorter hospital stay (3.1 [3.0-4.0] vs. 4.5 [4.0-6.0] days, P = 0.019), and fewer complications (0 vs. 4 cases). Univariate analysis showed that depth of the niche (P = 0.021) the mild adhesiolysis score (P = 0.035) and moderate adhesiolysis score (P = 0.013) were associated with the bladder injury. Multivariate analysis showed that the moderate adhesiolysis score (P = 0.029; 95% confidence interval, 1.318-3.526) was the strongest independent predictor of bladder injury. CONCLUSION: This study confirmed the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scars.


Assuntos
Cesárea/efeitos adversos , Cicatriz/cirurgia , Laparoscopia/métodos , Vagina/cirurgia , Adulto , Feminino , Humanos , Gravidez , Estudos Retrospectivos
13.
Onco Targets Ther ; 12: 8275-8286, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632077

RESUMO

BACKGROUND: Endometrial cancer (EC) is the most common gynecological malignancy with high incidence of metastasis, while the mechanism of metastasis in EC is not clear. METHODS: Immunohistochemistry and real-time PCR assays were used to assess expression of SOX17 in paraffin-embedded tissues from EC patients and in EC cells. The migration of EC cells was assessed by wound-healing and Transwell assays as well as in an in vitro study of nude mice. In addition, the expression of specific proteins was analyzed by Western blot. RESULTS: We observed that SOX17 expression levels were relatively high in stage I EC specimens, and were significantly correlated with the epithelial cadherin (E-cadherin) and ß-catenin expression. Additionally, stage II EC patients whose specimens had relatively high SOX17 expression levels had better outcomes. Wound-healing and Transwell assays and in vivo murine experiments revealed that SOX17 inhibited EC cell migration. Meanwhile, SOX17 increased expression of E-cadherin and decreased expression of ß-catenin and proteins in the Wnt signaling pathway. Moreover, LiCl (ß-catenin activator) enhanced the regulatory effects of SOX17 on the expression of E-cadherin, promigratory cadherin, vimentin, and proteins in the Wnt signaling pathway, while XAV93920 (ß-catenin inhibitor) exerted the opposite effect. The SOX17 N-terminus was proved to be necessary for these effects. Mechanistic investigations suggested SOX17 inhibits EC cell migration by inactivating the Wnt/ß-catenin-epithelial mesenchymal transition (EMT) axis in EC cells. CONCLUSION: We uncovered a common SOX17-ß-catenin-EMT mechanism underlying EC cell migration.

14.
Onco Targets Ther ; 12: 2235-2245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988628

RESUMO

OBJECTIVE: The aim of this study was to examine the effect of TRIB3 on proliferation, apoptosis, and migration of endometrial cancer (EC) cells and explore the relationship between TRIB3 and AKT signaling pathway in EC progression. METHODS: Immunohistochemical analysis was performed to measure the expression level of TRIB3 in normal endometrium tissues and EC tissues. Overexpression and shRNA knockdown techniques were applied by transfecting EC cells (ISK and AN3CA), and the effect of TRIB3 on EC cell biological behaviors was evaluated. Cell Counting Kit-8 and colony formation assays were utilized to investigate EC cell proliferation ability, and flow cytometry was performed to assess the apoptosis of EC cells. Moreover, the migration and invasion of EC cells were detected by transwell assay, and the levels of MMP-2 and MMP-9 were measured by ELISA. Additionally, Western blot analysis was carried out to determine the levels of AKT and p-AKT. RESULTS: The expression level of TRIB3 was higher in EC than normal endometrium tissues, and its overexpression promoted apoptosis and suppressed proliferation of EC cells. Furthermore, TRIB3 retarded the migration and invasion of EC cells and decreased the levels of MMP-2 and MMP-9. Conversely, TRIB3 inhibition enhanced the expression levels of MMP-2 and MMP-9, and proliferation and migration of EC cells but suppressed their apoptosis. Similarly, TRIB3 overexpression reduced while its knockdown increased the level of p-AKT. CONCLUSION: TRIB3 inhibited proliferation and migration and promoted apoptosis of EC cells probably through regulating AKT signaling pathway.

15.
Int J Surg ; 52: 40-43, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29455045

RESUMO

BACKGROUND: Pelvic organ prolapse (POP) is a common disease in women. The aim of this research was to evaluate the safety, efficacy and complication of transvaginal modified sacrospinous ligament fixation with mesh using for the treatment of vaginal vault prolapse. MATERIALS AND METHODS: This was a prospective study including information from 60 symptomatic women with anterior-apical pelvic floor prolapse. The patients underwent transvaginal modified sacrospinous ligament fixation combined with anterior vaginal wall mesh between May 2014 and Sep 2015. The perioperative data including clinical characteristic, operation time, blood loss, and surgical complications were collected at 1 year and 2 years. During a 2-year follow-up, the primary outcome evaluation included Pelvic organ prolapse Quantification system (POP-Q), Incontinence Quality of Life scale (I-QoL), the Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and the Pelvic Floor Distress Inventory, short form 20 (PFDI-20). RESULTS: The mean follow-up time was 2 years (range 24-37 months). The patients' mean age was 66.75 ±â€¯6.44. Of 60 patients who were enrolled in this research, 26 patients had severe stress urinary incontinence (SUI). The mean operation time was 99.14 ±â€¯19.60 min and the mean estimated blood loss was 73.83 ±â€¯41.05 ml. The rate of anatomical success was 98.3% and one patient had a recurrence. The POP-Q point measurements were evaluated preoperatively and postoperatively (P < 0.001). Moreover, the quality of life and sexual activity were all improved postoperatively via I-QoL, PISQ-12 and PFDI-20 scores (P < 0.001). There was no injury to the rectum, bladder, major pelvic vessels and pudendal nerves. However, 18 patients had postoperative complications. CONCLUSIONS: This study showed that transvaginal modified sacrospinous ligament fixation with mesh might be performed easily and might be a safe surgery for elderly patients whose requirements for sexual life were relatively low. Further researches were required to investigate its long-term efficacy.


Assuntos
Diafragma da Pelve/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos , Idoso , Feminino , Humanos , Ligamentos/cirurgia , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Vagina/cirurgia
16.
Sci Rep ; 7(1): 18042, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29273791

RESUMO

The introduction of the concept of gradient force and scattering and absorption force is an important milestone in optical trapping. However the profiles of these forces are usually unknown, even for standard setups. Here, we successfully calculated them analytically via multipole expansion and numerically via Mie theory and fast Fourier transform. The former provides physical insight, while the latter is highly accurate and efficient. A recipe to create truly conservative energy landscapes is presented. These may open up qualitatively new features in optical manipulation.

17.
Oncotarget ; 7(18): 25712-25, 2016 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-27015552

RESUMO

Epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) acted as a tumor suppressor in endometrial carcinoma (EC). However, the correlation between EFEMP1 and estrogen is unknown. Here, we reported that the expression of EFEMP1 was conversely associated with ERα in endometrial carcinoma tissues. In endometrial carcinoma cells, estrogen/ERα signaling significantly suppressed the expression of EFEMP1. Moreover, chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assays demonstrate that estrogen/ERα bound to the estrogen response element (ERE) located in EFEMP1 promoter and repressed its expression. Besides, in vitro and in vivo, EFEMP1 could remarkably suppress the expression of epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail and the Wnt/ß-catenin target genes like Cyclin-D1 and c-Myc, which could be restored when EFEMP1 was silenced. In addition, XAV93920 (the inhibitor of the Wnt/ß-catenin pathway) blocked and LiCl (the activator of the Wnt/ß-catenin pathway) enhanced the effect of EFEMP1 on EMT. In conclusion, we demonstrated that estrogen/ERα signal suppresses EFEMP1. Besides, EFEMP1 inhibits EMT via interfering the Wnt/ß-catenin signaling.


Assuntos
Neoplasias do Endométrio/patologia , Transição Epitelial-Mesenquimal/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Via de Sinalização Wnt/fisiologia , Animais , Neoplasias do Endométrio/metabolismo , Receptor alfa de Estrogênio/metabolismo , Estrogênios/metabolismo , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Nus
18.
Mol Med Rep ; 10(6): 3289-95, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25310186

RESUMO

We previously reported frequent loss of microRNA­218 (miR­218) in human cervical cancer, which was associated with tumor progression and poor prognosis. In this study, we investigated whether restoration of the miR­218 level is a valid strategy for the treatment of cervical cancer. The expression of miR­218 in cervical cancer samples and cell lines was quantified by reverse transcription TaqMan quantitative (RT­q)PCR. Overexpression of miR­218 was achieved by both transient and stable transfection, using a miR­218 mimic and a miR­218­expressing plasmid, respectively. Alterations in cellular proliferation and cell­cycle progression were measured by the MTT assay and flow cytometry analysis. Nude mice bearing SiHa xenografts were used to investigate the functions of miR­218 and carboplatin on tumor growth and weight. The expression of cycle­related proteins was detected by western blotting and immunohistochemical staining. In vitro, miR­218 significantly inhibited cellular growth in all four cell lines tested (P=0.021 for CaSki, P=0.009 for HeLa, P=0.016 for SiHa, and P=0.029 for C33A). Overexpression of miR­218 induced G1 phase arrest and reduced expression of cyclin D1 and CDK4. In vivo, restoration of miR­218 notably inhibited tumor growth and decreased tumor weight. In primary cultured samples, tumors with high levels of miR­218 were more sensitive to carboplatin (R2=0.3319, P=0.0026); consistently, miR­218 overexpression suppressed tumor growth, induced cell­cycle arrest, and reduced the cyclin D1 level. Based on these and previous results, we conclude that restoration of the miR­218 level inhibits the growth of cervical cancer cells both in vitro and in vivo; furthermore, overexpression of miR­218 sensitizes cervical cancer cells to carboplatin. Our findings suggest a novel therapy for cervical cancer based on miR­218, especially in patients with reduced levels of miR­218.


Assuntos
Pontos de Checagem da Fase G1 do Ciclo Celular/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclina D1/genética , Quinase 4 Dependente de Ciclina/genética , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transfecção/métodos
19.
PLoS One ; 8(6): e67458, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23840707

RESUMO

OBJECTIVE: EFEMP1, the epidermal growth factor-containing fibulin-like extracellular matrix protein 1, functions as an oncogene or a tumor suppressor depending on the cancer types. In this study, we aim to determine whether EFEMP1 affects the tumorigenesis and progression of endometrial carcinoma. METHODS: The expression of EFEMP1 was investigated using immunohistochemistry in a panel of normal endometrium (n = 40), atypical hyperplasia (n = 10) and endometrial carcinoma tissues (n = 84). Methylation status of the EFEMP1 promoter was detected by methylation-specific PCR (MSP) and bisulphite genomic sequencing. Up- or down-regulation of EFEMP1 were achieved by stable or transient transfection with pCMV6/GFP/Neo-EFEMP1 or pGPU6/GFP/Neo-shEFEMP1 respectively. Effects of EFEMP1 on tumor proliferation, invasion and migration were evaluated by MTT, plate colony formation, Transwell and wound healing assay. The nude mouse tumor xenograft assay was used to investigate function of EFEMP1 in vivo. RESULTS: Compared with normal endometrium (32/40) and atypical hyperplasia (7/10), EFEMP1 expression was much lower in endometrial carcinoma tissues (16/84) (P<0.001 and P = 0.02). EFEMP1 promoter was hypermethylated in endometrial carcinoma tissues (67%) as compared to normal tissue (10%) and down-regulation of EFEMP1 was associated with promoter hypermethylation. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC) and/or trichostatin A (TSA) altered EFEMP1 methylation status, and restored EFEMP1 expression. Moreover, EFEMP1 decreased secretion of MMPs and inhibited tumor cell proliferation, metastasis and invasion in vitro and suppressed tumorigenesis in nude mice. Besides, EFEMP1 increased expression of E-cadherin and suppressed expression of vimentin in endometrial carcinoma. CONCLUSION: EFEMP1 is a new candidate tumor suppressor gene in endometrial carcinoma, and is frequently silenced by promoter hypermethylation. It could inhibit tumor growth and invasion both in vitro and in vivo. Our findings propose that targeting EFEMP1 might offer future clinical utility in endometrial carcinoma.


Assuntos
Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Epigênese Genética/genética , Proteínas da Matriz Extracelular/genética , Animais , Caderinas/genética , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Metilação de DNA/genética , Progressão da Doença , Regulação para Baixo/genética , Hiperplasia Endometrial/genética , Hiperplasia Endometrial/patologia , Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor , Humanos , Metaloproteinases da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Regiões Promotoras Genéticas/genética , Vimentina/genética
20.
Oncol Rep ; 27(5): 1488-96, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22327423

RESUMO

Obesity is a well-established risk factor for endometrial cancer, due in part to the adipokines generated by adipose tissue, such as adiponectin (also known as Acrp30) and leptin, which are associated with many endocrine-related cancers. Recent reports suggested that Acrp30 inhibits leptin-stimulated cell proliferation in HEC-1A and RL95-2 endometrial cancer cell lines, and that the serum leptin/Acrp30 ratio plays an important role in endometrial cancer development. We explored whether Acrp30 could reverse the leptin-induced metastasis phenotype in the SPEC-2 endometrial cancer cell line. Transcripts for Acrp30 receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rb) were detected by quantitative real-time RT-PCR (qRT-PCR) in six endometrial cancer cell lines. Leptin (1 µg/ml) treatment stimulated SPEC-2 cell proliferation by inducing cell cycle arrest and apoptosis, while Acrp30 (10 µg/ml) treatment inhibited the growth of SPEC-2 cells. Importantly, Acrp30 was able to inhibit leptin-induced SPEC-2 cell proliferation. Leptin promoted SPEC-2 cell invasion in a Matrigel transwell assay, while Acrp30 partly suppressed the invasion stimulated by leptin. To investigate the molecular mechanism underlying this phenomenon, we monitored the AMPK and JAK/STAT3 signaling pathways by western blotting and cell immunofluorescence. Acrp30 reduced leptin-induced STAT3 phosphorylation and nuclear translocation via activation of the MAPK pathway. AG490 (JAK/STAT3 inhibitor) reduced MMP-2 and MMP-9 protein levels in cells treated with leptin, while IL-6 (JAK/STAT3 stimulator) and Compound C (AMPK inhibitor) elevated MMP-2 and MMP-9 protein levels in cells treated with Acrp30. In conclusion, we demonstrated that Acrp30 effectively reversed the invasion stimulated by leptin, and AMPK and JAK/STAT3 pathways mediated the invasive phenotype of SPEC-2 cells.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/farmacologia , Neoplasias do Endométrio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Janus Quinases/metabolismo , Leptina/farmacologia , Proteínas de Membrana/metabolismo , Fator de Transcrição STAT3/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Ativação Enzimática/efeitos dos fármacos , Feminino , Humanos , Metástase Neoplásica , Transporte Proteico/efeitos dos fármacos , Receptores de Adiponectina/genética , Receptores para Leptina/genética , Transdução de Sinais/efeitos dos fármacos
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