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1.
Artigo em Inglês | MEDLINE | ID: mdl-31520876

RESUMO

OBJECTIVES: To determine the risk factors for development of caesarean scar defect (CSD), compare the efficacy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for CSD assessment, and investigate the association between CSD size and clinical symptoms. STUDY DESIGN: One hundred and eighty-nine women with CSD and 378 women without CSD with a history of caesarean section (CS) at the Obsterics and Gynaecology Hospital of Fudan University between January 2008 and February 2016 were enrolled. The potential risk factors for CSD were investigated using multivariate logistic regression analysis. TVS and MRI were performed for CSD measurements, including residual myometrial thickness, and depth, length and width of CSD. Associations between CSD size by TVS/MRI and symptoms were evaluated. RESULTS: CS time ≥85 min, peripartum fever or infection, and retroflexed uterus were risk factors for CSD, and age at last CS < 30 years, intraoperative blood loss <150 ml and double-layer closure were protective factors for CSD. Prolonged menstruation, dysmenorrhoea, chronic pelvic pain and infertility were the main clinical manifestations. Women with a larger CSD presented with more prolonged menstruation. Compared with TVS, measurements by MRI showed better prediction of the clinical symptoms of CSD. CONCLUSIONS: Various factors contribute to the development of CSD. Prevention of peripartum infection, reduction of CS time, reduction of blood loss and more careful uterine closure are needed to decrease the risk of developing CSD. MRI is a reliable method for the diagnosis and measurement of CSD, and can be utilized in clinical practice.

2.
Oncol Rep ; 41(5): 2790-2802, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30864736

RESUMO

Protein phosphatase of regenerating liver­3 (PRL­3) is considered to be metastasis­associated phosphatase and is associated with a poor prognosis. Additionally, tumor­associated macrophages (TAMs) participate in cancer progression. A previous study demonstrated that PRL­3 promotes invasion and metastasis by inducing TAM infiltration. However, the underlying mechanism has not been elucidated. In the present study, western blot analysis, polymerase chain reaction, immunohistochemistry, ELISA, mouse model experiments and functional experiments were performed to confirm that the interaction between TAMs and colorectal cancer (CRC) cells induced epithelial­mesenchymal transition (EMT)­associated features in CRC cells by activating mitogen­activated protein kinase (MAPK) pathways in TAMs and upregulating the expression of interleukin (IL)­6 and IL­8. The neutralization of IL­6 and IL­8 reduced EMT and the invasive and migratory abilities of CRC cells. Therefore, IL­6 and IL­8 were considered important factors in EMT, and in CRC invasion and metastasis. In addition, increased angiogenesis was observed after TAMs were co­cultured with CRC cells that overexpress PRL­3. Vascular endothelial growth factor­A was significantly upregulated, and the nuclear factor­κB (NF­κB) signaling pathway was activated in CRC cells after co­culture. Moreover, nude mice injected with CRC cells with high PRL­3 expression levels tended to generate larger xenografts. Immunohistochemistry results from xenografted CRC cells overexpressing PRL­3 also confirmed the activation of MAPK pathways in xenografts. Overall, the findings indicate that PRL­3 promotes CRC cell invasion and metastasis by activating MAPK pathways in TAMs to initiate the EMT, and PRL­3 promotes angiogenesis by activating the NF­κB pathway in CRC cells.


Assuntos
Neoplasias Colorretais/patologia , Macrófagos/imunologia , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/patologia , Proteínas Tirosina Fosfatases/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/imunologia , Transição Epitelial-Mesenquimal/imunologia , Humanos , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Invasividade Neoplásica/imunologia , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/imunologia , Neovascularização Patológica/imunologia , Proteínas Tirosina Fosfatases/imunologia , Microambiente Tumoral/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
J Mol Cell Biol ; 11(5): 421-432, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30215728

RESUMO

Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin αV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin αV and SIN3B expressions in HCC patients and tumor cell lines with different metastatic potentials. Overexpression of SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed when integrin αV expression was silenced. Interestingly, SIN3B stimulated integrin αV subunit promoter activity only in the presence of sulfatide. Importantly, SIN3B was identified in the complex with sulfatide by mass spectrometry. Fat blot assay indicated that SIN3B specifically interacted with sulfatide. Molecular modeling suggested that sulfatide induced the conformational change of SIN3B from compacted α-helices to a relaxed ß-sheet in PAH2 domain. The data of immunoprecipitation and ChIP assay indicated that altered SIN3B lost the binding affinity with MAD1 and HDAC2, which reduced the recruitment of HDAC2 on integrin αV gene promoter and prevented the deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B promoted the transcriptional activation of the integrin αV subunit gene promoter by reducing interaction with HDAC2.

4.
Arch Gynecol Obstet ; 297(3): 775-784, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29362924

RESUMO

PURPOSE: Ovarian conservation is controversial in patients with cervical adenocarcinoma due to the risk of ovarian metastasis. The aim of this study is to evaluate the association of ovarian conservation with survival outcomes in young patients with T1N0M0 cervical adenocarcinoma. METHODS: Women who were 45 years of age or younger with T1N0M0 cervical adenocarcinoma from 1988 to 2013 recorded in the Surveillance, Epidemiology, and End Results (SEER) database were included. Propensity score weighting was used to balance the intragroup differences. Cause-specific survival (CSS) and overall survival (OS) were compared using Kaplan-Meier estimates. A multivariate Cox model was used to adjust for covariates including propensity score. A stratified analysis was then conducted. RESULTS: Totally, 1090 (79.7%) patients underwent oophorectomy and 278 (20.3%) patients whose ovaries were preserved were identified. Patients with preserved ovaries were younger, with a lower T classification and less likely to undergo pelvic lymphadenectomy (all p < 0.05). After propensity weighting, ovarian conservation group had better cause-specific survival (CSS) (5-year 98.8 versus 97.1%, 10-year 98.0 versus 95.2%, p = 0.0370) and overall survival (OS) (5-year 98.8 versus 97.1%, 10-year 96.5 versus 93.5%, p = 0.0025). After adjustment, the CSS benefit of ovarian conservation was marginally significant (p = 0.051) and OS benefit was still significant (p = 0.006). Stratified analysis showed that the CSS benefit was found in T1b classification (HR, 0.23; 95% CI 0.06-0.89, p = 0.033) and histological grade > 1 (HR 0.12; 95% CI 0.02-0.87; p = 0.035). CONCLUSION: Among young women with T1N0M0 cervical adenocarcinoma, ovarian conservation is associated with better survival.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma Adenoescamoso/cirurgia , Tratamentos com Preservação do Órgão , Neoplasias do Colo do Útero/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma Adenoescamoso/mortalidade , Carcinoma Adenoescamoso/patologia , Bases de Dados Factuais , Feminino , Preservação da Fertilidade/métodos , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ovariectomia , Ovário/patologia , Ovário/cirurgia , Vigilância da População , Pontuação de Propensão , Sistema de Registros , Programa de SEER , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
5.
Mol Cancer Ther ; 17(1): 276-289, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29051319

RESUMO

Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAM) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer invasion and metastasis by inducing TAM infiltration remains unclear. In the current study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and colorectal cancer invasion and the underlying mechanism in colorectal cancer cells by overexpressing or silencing PRL-3. We found that PRL-3 upregulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. In addition, IHC analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV colorectal cancer tissues and were associated with a worse prognosis in colorectal cancer patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were cocultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca2+of TAMs to increase the expression of IL6 and IL8. In addition, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV colorectal cancer tissues and correlated with CCL26. Moreover, similar results were observed in vivo using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes colorectal cancer invasion and metastasis by upregulating CCL26 to induce TAM infiltration. Mol Cancer Ther; 17(1); 276-89. ©2017 AACR.


Assuntos
Quimiocina CCL26/imunologia , Neoplasias Colorretais/imunologia , Macrófagos/imunologia , Proteínas de Neoplasias/imunologia , Proteínas Tirosina Fosfatases/imunologia , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Células HT29 , Humanos , Macrófagos/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Transfecção
6.
J Obstet Gynaecol ; 37(8): 1076-1081, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28760055

RESUMO

Caesarean scar defect (CSD) can cause postmenstrual bleeding. Defect repair is an effective technique to improve this symptom, but there are still a few patients getting little improvement. This retrospective study evaluates the efficacy of scar repair and explores the factors associated with poor effect. In total, 123 patients were involved in the final analysis. All of them complained about menstruation period >7 days due to postmenstrual bleeding. Before surgery, 87.8% of patients had a menstruation period more than 10 days and 20.3% had a period more than 15 days. After surgery, a normal menstruation period (< =7 days) was achieved in 46.3% (95%CI 37.3%-55.6%) of patients and a menstruation period lasting no more than 10 days was achieved in 74.8% (95%CI 66.2%-82.2%). Through multivariate logistic analysis, four factors were found dependently associated with poor effect (defined as menstruation period >10 days after surgery): repeated caesarean section (OR 9.75, 95%CI 2.30-41.36, 0.002) was a risk factor, while defect volume >600 mm3 (OR 0.14, 95%CI 0.03-0.56, 0.006), interval from caesarean section to symptom emerging >3 months (OR 0.25, 95%CI 0.07-0.94, 0.041) and straight or retroflexed uterus (OR 0.19, 95%CI 0.05-0.79, 0.022) were protective factors. Impact statement What is already known on this subject? Caesarean scar defect can cause postmenstrual bleeding. Defect repair can improve this symptom, but there are still a few patients getting little improvement after surgery. What do the results of this study add? Defect volume >600 mm3, interval from caesarean section to symptom emerging >3 months and straight or retroflexed uterus are protective factors of poor effect (defined as menstruation period >10 days after surgery), and repeated caesarean section is a risk factor. What are the implications of these findings for clinical practice and/or further research? These findings may help in counselling the patients and in medical decision. Further researches are needed to explore other factors associated with surgical effect and build prediction models.


Assuntos
Cesárea/efeitos adversos , Cicatriz/cirurgia , Menstruação , Hemorragia Uterina/terapia , Adulto , Recesariana/efeitos adversos , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Hemorragia Uterina/epidemiologia
7.
Int J Oncol ; 51(4): 1271-1279, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28791350

RESUMO

Phosphatase of regenerating liver-3 (PRL-3) has been found to be overexpressed in liver metastases of colorectal cancer and rarely expressed in primary tumors, which plays an important role in the metastasis of colorectal cancer cells. Metabolism reprogramming has been found to be a hallmark of cancer cells, and aerobic glycolysis is a metabolic adaption for cancer cells and promotes cell proliferation. However, the association between PRL-3 and glycolysis in colorectal cancer cells is not well understood. In the present study, we explored the association between PRL-3 and glycolysis. We found that PRL-3 improved colorectal cancer cell glucose assumption, lactate production and reduced intracellular ROS levels. Besides, PRL-3 improved the expression of Glut1, HK2, PKM2 and LDHA, which are important glycolysis related molecules and enzymes. Moreover, we explored IL-8 mediated enhancement of glycolysis by PRL-3. More importantly, the proliferation and invasion of colorectal cancer cells were enhanced significantly by PRL-3 through improving glycolysis. Taken together, these results implicated the important role of PRL-3 in glycolysis metabolism through improving IL-8 secretion in colorectal cancer cells, and PRL-3 mediated glycolysis contributed to the promotion of cancer metastasis.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Interleucina-8/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Reprogramação Celular/fisiologia , Glicólise , Humanos , Invasividade Neoplásica , Espécies Reativas de Oxigênio/metabolismo
8.
Oncotarget ; 7(19): 27394-407, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27034164

RESUMO

Our previous study revealed that neuroendocrine differentiation in colorectal cancer is one of the important factors leading to worse prognosis. In this study, we apply immunohistochemical staining, Western-blot, RT-PCR and ELISA to investigate the underlying mechanism that how the neuroendocrine differentiation to affect the prognosis of colorectal cancer. The interaction of colorectal cancer cells, neuroendocrine-like cells and tumor-associated macrophages in colorectal cancer progress is also investigated. By analyzing 82 cases of colorectal cancer patients treated in our institution, we found that colorectal adenocarcinoma with neuroendocrine differentiation had increasing number of tumor-associated macrophages and worse prognosis. Further evaluation of cytology showed that neuroendocrine cells have the ability to recruit tumor-associated macrophages to infiltrate the tumor tissue, and the tumor-associated macrophages enhance the proliferation and invasion abilities of the colon cancer cells. Moreover, we confirmed that CXCL10 and CXCL11 are the key chemokines in neuroendocrine-like cells and they promote the chemotaxis activity of tumor-associated macrophages. The secretion of CXCL10 and CXCL11 by neuroendocrine-like cells can recruit tumor-associated macrophages to infiltrate in tumor tissues. The latter enhances the proliferation and invasion of colorectal cancer cell and lead to poor prognosis.


Assuntos
Adenocarcinoma/metabolismo , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/metabolismo , Neoplasias Colorretais/metabolismo , Macrófagos/metabolismo , Células Neuroendócrinas/metabolismo , Adenocarcinoma/patologia , Células CACO-2 , Linhagem Celular Tumoral , Proliferação de Células , Quimiotaxia , Neoplasias Colorretais/patologia , Feminino , Subunidade alfa de Hormônios Glicoproteicos/genética , Subunidade alfa de Hormônios Glicoproteicos/metabolismo , Células HT29 , Humanos , Masculino , Pessoa de Meia-Idade , Células Neuroendócrinas/patologia , Prognóstico
9.
Int J Mol Sci ; 16(8): 19401-18, 2015 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-26287184

RESUMO

The potential anti-neoplastic activity of terpenoids is of continued interest. In this study, we investigate whether methyl sartortuoate, a terpenoid isolated from soft coral, induced cell cycle arrest and apoptosis in a human colon cancer cell line. Culture studies found that methyl sartortuoate inhibited colon cancer cell (LoVo and RKO) growth and caused apoptotic death in a concentration- and time-dependent manner, by activation of caspase-8, caspase-9, caspase-3, p53 and Bax, and inactivation of B-cell lymphoma 2 (Bcl-2) apoptosis regulating proteins. Methyl sartortuoate treatment led to reduced expression of cdc2 and up-regulated p21 and p53, suggesting that Methyl sartortuoate induced G2-M arrest through modulation of p53/p21/cdc2 pathways. Methyl sartortuoate also up-regulated phospho-JNK and phospho-p38 expression levels. This resulted in cell cycle arrest at the G2-M phase and apoptosis in LoVo and RKO cells. Treatment with the JNK inhibitor SP600125 and the p38 MAPK inhibitor SB203580 prevented methyl sartortuoate-induced apoptosis in LoVo cells. Moreover, methyl sartortuoate also prevented neoplasm growth in NOD-SCID nude mice inoculated with LoVo cells. Taken together, these findings suggest that methyl sartortuoate is capable of leading to activation of caspase-8, -9, -3, increasing p53 and Bax/Bcl-2 ratio apoptosis through MAPK-dependent apoptosis and results in G2-M phase arrest in LoVo and RKO cells. Thus, methyl sartortuoate may be a promising anticancer candidate.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Colo/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Terpenos/uso terapêutico , Animais , Antozoários/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Transdução de Sinais/efeitos dos fármacos , Terpenos/isolamento & purificação , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
BMC Cancer ; 14: 330, 2014 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-24885636

RESUMO

BACKGROUND: Tumor-associated macrophages (TAMs) are known to promote cancer progression and metastasis through the release of a variety of cytokines. Phosphatase of regenerating liver (PRL-3) has been considered as a marker of colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL-3 can enhance the metastasis of CRC through the up-regulation of intermediate-conductance Ca2+-activated K+ (KCNN4) channel, which is dependent on the autocrine secretion of tumor necrosis factor-alpha (TNF-α). However, whether TAMs participate in the progression and metastasis of CRC induced by PRL-3 remains unknown. METHODS: We used flow cytometry, coculture, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, and immunofluorescence staining to determine the effect of TAMs on the ability of PRL-3 to promote invasiveness of CRC cells. RESULTS: In this study, we found that TAMs facilitated the metastasis of CRC induced by PRL-3. When TAMs were cocultured with CRC cells, the expression of KCNN4 was increased in TAMs and the invasion of CRC cells was enhanced. Furthermore, cytokines that were secreted by TAMs, such as IL-6 and IL-8, were also significantly increased. This response was attenuated by treating TAMs with the KCNN4 channel-specific inhibitor, 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34), which suggested that KCNN4 channels may be involved in inducing the secretion of IL-6 and IL-8 by TAMs and improving CRC cell invasiveness. Moreover, the expression of KCNN4 channels in TAMs was regulated through the NF-κB signal pathway, which is activated by TNF-α from CRC cells. Immunofluorescence analysis of colorectal specimens indicated that IL-6 and IL-8 double positive cells in the stroma showed positive staining for the TAM marker CD68, suggesting that TAMs produce IL-6 and IL-8. Increased numbers of these cells correlated with higher clinical stage. CONCLUSIONS: Our findings suggested that TAMs participate in the metastasis of CRC induced by PRL-3 through the TNF-α mediated secretion of IL-6 and IL-8 in a paracrine manner.


Assuntos
Movimento Celular , Neoplasias do Colo/enzimologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Macrófagos/enzimologia , Proteínas de Neoplasias/metabolismo , Comunicação Parácrina , Proteínas Tirosina Fosfatases/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Técnicas de Cocultura , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/antagonistas & inibidores , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , NF-kappa B/metabolismo , Invasividade Neoplásica , Bloqueadores dos Canais de Potássio/farmacologia , Regiões Promotoras Genéticas , Transdução de Sinais , Fatores de Tempo , Transfecção , Microambiente Tumoral , Fator de Necrose Tumoral alfa/metabolismo
11.
Asian Pac J Cancer Prev ; 14(10): 5775-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24289577

RESUMO

BACKGROUND: The gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine neoplasm. We summarized data in our centre to investigate the clinicopathological features, diagnostic methods, therapeutic approaches and prognosis for this neoplasm to increase knowledge of this disease in Asian populations. METHOD: A total of 122 patients treated at Sun Yet-san Memorial Hospital of Sun Yat-sen University between January 2000 and December 2011 were analyzed retrospectively. RESULTS: Pancreas was the most common site of involvement (65/122, 53.3%); this disease has no special symptoms; positive rates of chromogranin A (CgA) and synaptophysin (Syn) were 81.1% and 87.7%, respectively. The positive rate of Syn had statistical difference among the three grades, but not CgA. Some 68 patients had G1 tumors, 32 G2 tumors and 22 G3 tumors, and Chi-square test showed that higher grading was correlated with worse prognosis (χ2=32.825, P=0.0001). A total of 32 patients presented with distant metastasis, and 8 cases emerged during following up. Cox proportional hazards regression modeling showed that the tumor grade (P=0.01), lymphatic metastasis (P=0.025) and distant metastasis (P=0.031) were predictors of unfavorable prognosis. The overall 5-year survival rate was 39.6%, the 5-year survival rate of G1 was 55.7%, and the G2 and G3 were 34.2% and 0%, respectively. CONCLUSIONS: The incidence of gastroenteropancreatic neuroendocrine tumors has risen over the last 12 years. All grades of these diseases metastasize readily, and further research regarding the treatment of patients after radical surgery is needed to prolong disease-free survival.


Assuntos
Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/patologia , Grupo com Ancestrais do Continente Asiático , Cromogranina A/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/mortalidade , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Sinaptofisina/uso terapêutico
12.
Med Oncol ; 30(2): 566, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23572150

RESUMO

Studies have shown that phosphatase of regenerating liver-3 (PRL-3) promotes the invasion, migration, and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition (EMT). However, the mechanism by which PRL-3 induces tumor cell EMT is unknown. Our previous research revealed that PRL-3 promotes LoVo cell proliferation by up-regulating KCNN4 channels. In the current study, we explored the mechanism by which PRL-3 mediates EMT. We demonstrated that PRL-3 induced the expression of KCNN4 channels, leading to EMT and the down-regulation of E-cadherin. Further studies revealed that KCNN4 channels increased intracellular calcium levels and activated components of cell signaling downstream of calcium, including CaM-kinase II and glycogen synthase kinase-3 beta (GSK-3 beta), which increased Snail expression. Inhibiting KCNN4 with siRNA and TRAM-34, a specific inhibitor, restored E-cadherin expression and inhibited Snail expression. These results implicated the up-regulation of KCNN4 channels in the PRL-3-mediated induction of EMT and promotion of cancer metastasis.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Análise de Variância , Caderinas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Quinase 3 da Glicogênio Sintase/metabolismo , Histocitoquímica , Humanos , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/genética , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo
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