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1.
World J Gastrointest Oncol ; 13(11): 1709-1724, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34853645

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the most lethal malignancies worldwide. It is known that the proliferation of PC cells is a critical process in the disease. Previous studies have failed to identify the key genes associated with PC cell proliferation, using bioinformatic analysis, genome-wide association studies, and candidate gene testing. AIM: To investigate the function of the chromobox 8 (CBX8)/receptor substrate 1 (IRS1)/AKT axis in PC. METHODS: A genome-wide CRISPR-Cas9 screening was performed to select genes that could facilitate PC cell proliferation. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CBX8 in PC tissues and cells. The regulatory roles of CBX8 in cell proliferation, migration, and invasion were verified by in vivo and in vitro functional assays. RESULTS: CBX8 was upregulated in PC tissues and shown to drive PC cell proliferation. Higher expression of CBX8 was correlated with worse outcomes of PC patients from two independent cohorts comprising a total of 116 cases. CBX8 was also proved to serve as a promising therapeutic target for a PC xenograft model. We demonstrated that hypoxia-inducible factor (HIF)-1a induced CBX8 transcription by binding to the promoter of CBX8. CBX8 efficiently activated the PI3K/AKT signaling by upregulating insulin IRS1. CONCLUSION: CBX8 is a key gene regulated by HIF-1α, and activates the IRS1/AKT pathway, which suggests that targeting CBX8 may be a promising therapeutic strategy for PC.

2.
World J Gastroenterol ; 27(17): 1993-2014, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34007135

RESUMO

BACKGROUND: Previous studies have suggested that long non-coding RNAs (lncRNA) TP73-AS1 is significantly upregulated in several cancers. However, the biological role and clinical significance of TP73-AS1 in pancreatic cancer (PC) remain unclear. AIM: To investigate the role of TP73-AS1 in the growth and metastasis of PC. METHODS: The expression of lncRNA TP73-AS1, miR-128-3p, and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction. The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p. The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation, migration, and invasion abilities were verified by Cell Counting Kit-8, wound-healing, and transwell assays, as well as flow cytometry and Western blot analysis. The interactions among TP73-AS1, miR-128-3p, and GOLM1 were explored by bioinformatics prediction, luciferase assay, and Western blot. RESULTS: The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells. High TP73-AS1 expression was correlated with a poor prognosis. TP73-AS1 silencing inhibited PC cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. Mechanistically, TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p. CONCLUSION: Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis, which might provide a potential treatment strategy for patients with PC.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética
3.
J Surg Oncol ; 123 Suppl 1: S65-S75, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33646594

RESUMO

BACKGROUND AND OBJECTIVES: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature. METHODS: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence. RESULTS: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches. CONCLUSIONS: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.


Assuntos
Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pós-Operatório , Protectomia/métodos , Estudos Prospectivos , Neoplasias Retais/patologia , Resultado do Tratamento , Adulto Jovem
4.
World J Gastroenterol ; 26(19): 2349-2373, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32476798

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the deadliest cancers worldwide. PC metastasis involves a complex set of events, including epithelial-mesenchymal transition (EMT), that increase tumor cell invasiveness. Recent evidence has shown that hypoxia is a major EMT regulator in pancreatic cancer cells and facilitates metastasis; however, the mechanisms remain elusive. AIM: To investigate the role of miR-301a in hypoxia-induced EMT in PC cells. METHODS: Real-time PCR and Western blot analysis were used to detect the expression of miR-301a and EMT markers in PDAC cells cultured in hypoxic and normoxic conditions. Western blot analysis was used to detect the expression of EMT markers in PDAC cells with miR-301a overexpression. Wound healing assay and Transwell assay were used to detect the migration capabilities of PDAC cells with miR-301a overexpression and knockout. Luciferase assay was used to detect the miR-301a promoter and the 3' untranslated region activity of TP63. Orthotopic PC mouse models were used to study the role of miR-301a in metastasis of PDAC cells in vivo. In situ hybridization assay was used to detect the expression of miR-301a in PDAC patient samples (adjacent paratumor and paired tumor tissues). . RESULTS: Hypoxic environment could directly promote the EMT of PC cells. The expression level of miR-301a was increased in a HIF2α dependent manner in hypoxia-cultured CFPAC-1 and BxPC-3 cells. Overexpression of miR-301a enhanced the hypoxia-induced EMT of PC cells, while knocking out miR-301a result in the suppression of hypoxia-induced EMT. TP63 was a direct target of miR-301a and involved in the metastatic process of PC cells. Furthermore, miR-301a upregulation facilitated PDAC distant metastasis and lymph node metastasis in vivo. Additionally, miR-301a overexpression was indicative of aggressive clinicopathological behaviors and poor prognosis. CONCLUSION: The newly identified HIF-2α-miR301a-TP63 signaling pathway may play a crucial role in hypoxia-induced EMT in PDAC cells.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Ductal Pancreático/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Regiões 3' não Traduzidas/genética , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Hipóxia Celular/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Masculino , Camundongos , MicroRNAs/análise , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Regiões Promotoras Genéticas/genética , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Guang Pu Xue Yu Guang Pu Fen Xi ; 37(3): 836-40, 2017 Mar.
Artigo em Chinês, Inglês | MEDLINE | ID: mdl-30160391

RESUMO

In order to realize rapid identification of dried red jujubes, this paper proposes a method based on near-infrared hyperspectral imaging technology. The near-infrared hyperspectral images (1 000~1 600 nm) of 240 samples in total from 4 cultivars of dried red jujubes will be acquired. The samples are to be divided into the calibration set and the prediction set in the ratio of 2∶1. 7, 8, 10 effective wavelengths are to be selected by principal component analysis(PCA), x-loading weight(x-LW)and successive projection algorithm(SPA) respectively. The dimensionality of original hyperspectral images will be reduced with PCA, and texture features of the first principal component image are to be extracted with gray-level co-occurrence matrix(GLCM).The partial least squares-discriminant analysis(PLS-DA), back propagation neural network(BPNN)and least square support vector machine(LS-SVM) are to be applied to build identification models with the selected effective wavelengths, texture features and fusion of the former two features. The identification rates of the models based on fusion features will be higher than those of models based on the spectral features or texture features respectively. The BPNN models based on the fusion features will obtain the best results, whose identification rates of prediction set are to be 100%. The results in this paper indicate that the near-infrared hyperspectral imaging technology has great potential to identify the dried red jujubes rapidly.

6.
Oncol Lett ; 12(4): 2445-2450, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27698811

RESUMO

The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques. In gastric cancer tissues, the expression of FoxM1 and E-cadherin was strongly positive, but it was weak in normal gastric mucosa. Overexpression of FoxM1 was evident in gastric cancer, and was associated with poor tumor differentiation (P<0.05), advanced tumor state (P<0.05) and lymph node (or distant) metastasis (P<0.05), whereas E-cadherin had the opposite effects. Furthermore, the correlation between FoxM1 and E-cadherin expression in gastric cancer tissue was negative. In conclusion, the high FoxM1 expression and low E-cadherin expression in gastric cancer tissue suggests that these proteins play a critical role in the development and progression of gastric cancer.

7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(3): 795-9, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27400526

RESUMO

Effective cultivation of the microalgae is the key issue for microalgal bio-energy utilization. In nutrient rich culture conditions, the microalge have a fast growth rate, but they are more susceptible to environmental pollution and influence. So to monitor the the growth process of microalgae is significant during cultivating. Hyperspectral imaging has the advantages of both spectra and image analysis. The spectra contain abundant material quality signal and the image contains abundant spatial information of the material about the chemical distribution. It can achieve the rapid information acquisition and access a large amount of data. In this paper, the authors collected the hyperspectral images of forty-five samples of Chlorella sp., Isochrysis galbana, and Spirulina sp., respectively. The average spectra of the region of interest (ROI) were extracted. After applying successive projection algorithm (SPA), the authors established the multiple linear regression (MLR) model with the spectra and corresponding biomass of 30 samples, 15 samples were used as the prediction set. For Chlorella sp., Isochrysis galbana, and Spirulina sp., the correlation coefficient of prediction (r(pre)) are 0.950, 0.969 and 0.961, the root mean square error of prediction (RMSEP) for 0.010 2, 0.010 7 and 0.007 1, respectively. Finally, the authors used the MLR model to predict biomass for each pixel in the images of prediction set; images displayed in different colors for visualization based on pseudo-color images with the help of a Matlab program. The results show that using hyperspectral imaging technique to predict the biomass of Chlorella sp. and Spirulina sp. were better, but for the Isochrysis galbana visualization needs to be further improved. This research set the basis for rapidly detecting the growth of microalgae and using the microalgae as the bio-energy.


Assuntos
Biomassa , Chlorella/crescimento & desenvolvimento , Haptófitas/crescimento & desenvolvimento , Análise Espectral , Spirulina/crescimento & desenvolvimento , Algoritmos , Modelos Teóricos
8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(2): 511-4, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-27209759

RESUMO

The seed purity is an important indicator of seed quality. The paper proposes a visual identification method of corn seed based on the near-infrared (874~1,734 nm) hyperspectral image technology. Hyperspectral image data of 4 cultivars of a total of 384 corn seed samples will be acquired. Then 288 of samples are to be selected randomly as the calibration set, and the remaining 96 samples will be used for the prediction set. After inspection of the near-infrared spectral curves, 7 effective wavelengths (EWs) are to be selected by successive projection algorithm (SPA). And then 7 EWs of the calibration set will be used as input to build a partial least squares (PLS) model. Good results are to be obtained with Rc = 0.917 7, RMSECV = 0.444 2; Rcv = 0.911 5, RMSECV = 0.459 9. And the total identification rate of the developed PLS model will be 78.5% for the calibration set and 70.8% for the prediction set. Finally, average spectral data of each corn seed in a hyperspectral image will be extracted by image process technology, and used as input of the developed SPA-PLS model. In the produced identification map, different colors are to be used to represent different predicted cultivars. 3 mixture samples of corn seeds will be identified, and help to achieve satisfied visual effects. The result indicates that, by means of the visual identification technology we could intuitively observe the distribution of corn seeds of different cultivars in mixture samples. The research provides help for the identification and screening of seeds in agricultural production.


Assuntos
Sementes , Análise Espectral , Zea mays
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(11): 3572-7, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30198685

RESUMO

In china, researches on Raman spectroscopy in terms of foodstuff mainly focus on carbohydrates, fatty acids, proteins and vitamins. Conventional methods for determining the carotenoids content require the extraction of the samples as well as other cleanup steps. In this work, Raman spectroscopy is applied to get the measured value form loquats with different mature stage which are compared with the reference value get from High Performance Liquid Chromatography (HPLC),in order to find new, fast, and nondestructive calibration methods for quantification of ß-carotene content in loquat fruits. Least Squares Support Vector Machine and Partial least squares data processing methods are used to analyze the Raman spectra while PLS model has a prediction quality with the correlation coefficient of 0.845; the root-mean-square error of 0.022 µg·g(-1) and LS-SVM model has a better prediction quality with the correlation coefficient of 0.910 with the root-mean-square error of 0.058 µg·g(-1).


Assuntos
Eriobotrya/química , Análise Espectral Raman , beta Caroteno/análise , Calibragem , Carotenoides , Ácidos Graxos , Frutas , Análise dos Mínimos Quadrados , Espectroscopia de Luz Próxima ao Infravermelho , Máquina de Vetores de Suporte
10.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(5): 1352-7, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-30001004

RESUMO

Microalgae based biodiesel production requires a large amount of lipid accumulation in the cells, and the accumulation is greatly influenced by the environment. Therefore, it is necessary to find fast and non-destructive methods for lipid change detection. In this paper, Chlorella sp. was adopted as the objective, which was cultured under different light condition consisted of red and blue lights with different proportion. We applied the visible near-infrared spectroscopy (Vis/NIRs) technique to detect the dynamic change of lipid during the microalgae growth processes and utilized hyperspectral imaging technology for visualization of lipid distribution in the suspension. The transmittance and reflectance spectra of microalgae were acquired with Vis/NIRs and hyper-spectroscopy, respectively. In the comparison of the transmittance and reflectance spectra, they showed some different characteristics. Meanwhile it also varied in terms of the number and the area of feature wavelengths obtained by successive projections algorithm (SPA) based on the different spectra. But the established multiple linear regression (MLR) model for lipid content prediction had similar results with rpre of 0.940, RMSEP of 0.003 56 and rpre of 0.932, RMSEP of 0.004 23, respectively. Based on the predictive model, we obtained the spectra and analyzed the lipid dynamic change in microalgae in one life cycle. In the life cycle, the lipid content in Chlorella sp. was relatively stable from the beginning of inoculation to exponential phase, the increase and accumulation of lipid phenomenon occurred in the late exponential phase. Combined with the MLR model and the hypersepctral images, we studied the visualization result of microalgae suspension in the steady phase. The stimulated images showed that the microalgae with higher lipid content appeared gathering. This study compared the difference and the feasibility of the Vis/NIRs and hyperspectral imaging technique in lipid content detection applied in microalgae growing microalgae. The results are meaningful for the fast and non-destructive detection of the growth information of microalgae. It has boththeoretical and practical significance for developing microalgal culture and harvest strategy in practice.


Assuntos
Chlorella , Microalgas , Algoritmos , Biocombustíveis , Biomassa , Lipídeos , Espectroscopia de Luz Próxima ao Infravermelho
11.
Hepatobiliary Pancreat Dis Int ; 14(2): 132-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25865684

RESUMO

BACKGROUND: The role of diabetes mellitus (DM) in pancreatic fistula (PF) or clinical relevant PF (CR-PF) after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD) is unclear. We conducted a meta-analysis to investigate the relationship between DM and PF or CR-PF. DATA SOURCES: Embase, MEDLINE and Cochrane databases were searched systematically for relevant articles from January 2005 to June 2013. The selected studies that examined clinical risk factors of PF or CR-PF were included. We created pooled estimates for our outcomes using the random-effects model. RESULTS: Sixteen observational clinical studies were included. Pooling of PF rates from ten studies revealed that DM was associated with a decreased risk of PF (P=0.01). CR-PF rates from 8 studies showed no significant difference between DM and control group (P=0.14). CONCLUSIONS: DM is not a risk factor for PF in patients undergoing PD or PPPD. On the contrary, patients without DM are at a higher risk of PF because the pancreases in these patients have more fatty tissue and the pancreas is soft.


Assuntos
Diabetes Mellitus/epidemiologia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Humanos , Período Pré-Operatório , Fatores de Proteção
12.
World J Gastroenterol ; 21(48): 13532-41, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26730165

RESUMO

AIM: To assess the diverse immediate and long-term clinical outcomes, a retrospective comparison between laparoscopic and conventional operation was performed. METHODS: A total number of 916 clinical cases, from January 2006 to December 2013 in our hospital, were analyzed which covered 492 patients underwent the laparoscopy in radical resection (LRR) and 424 cases in open radical resection (ORR). A retrospective analysis was proceeded by comparing the general information, surgery performance, pathologic data, postoperative recovery and complications as well as long-term survival to investigate the diversity of immediate and long-term clinical outcomes of laparoscopic radical operation. RESULTS: There were no statistically significance differences between gender, age, height, weight, body mass index (BMI), tumor loci, tumor node metastasis stages, cell differentiation degree or American Society of Anesthesiologists scores of the patients (P > 0.05). In contrast to the ORR group, the LRR group experienced less operating time (P < 0.001), a lower blood loss (P < 0.001), and had a 2.44% probability of conversion to open surgery. Postoperative bowel function recovered more quickly, analgesic usage and the average hospital stay (P < 0.001) were reduced after LRR. Lymph node dissection during LRR appeared to be slightly more than in ORR (P = 0.338). There were no obvious differences in the lengths and margins (P = 0.182). And the occurrence rate in the two groups was similar (P = 0.081). Overall survival rate of ORR and LRR for 1, 3 and 5 years were 94.0% and 93.6% (P = 0.534), 78.1% and 80.9% (P = 0.284) and 75.2% and 77.0% (P = 0.416), respectively. CONCLUSION: Laparoscopy as a radical operation for rectal cancer was safe, produced better immediate outcomes. Long-term survival of laparoscopy revealed that it was similar to the open operation.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Retais/cirurgia , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Telemed J E Health ; 20(2): 157-60, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23758077

RESUMO

BACKGROUND: Continuing medical education (CME) is an effective way for practicing physicians to acquire up-to-date clinical information. MATERIALS AND METHODS: We conducted four CME seminars in 2007-2010 endorsed by the Chinese Medical Association Council on Medical Education. Overseas telelectures and live case demonstrations were introduced in each seminar via telemedicine based on a digital video transport system. Network stability and packet loss were recorded. An anonymous mini-questionnaire was conducted to evaluate the satisfaction of attendees regarding the image and sound quality, content selection, and overall evaluation. RESULTS: Four telelectures and five live case demonstrations were successfully conducted. Stability of the network was maintained during each videoconference. High-quality videos of 720 × 480 pixels at the rate of 30 frames per second were shown to the entire group of attendees. The time delay between Shanghai and Fukuoka, Japan, was only 0.3 s, and the packet loss was 0%. We obtained 129 valid responses to the mini-questionnaire from a total of 146 attendees. The majority of the attendees were satisfied with the quality of transmitted images and voices and with the selected contents. The overall evaluation was ranked as excellent or good. CONCLUSIONS: Videoconferences are excellent channels for CME programs associated with laparoscopic training.


Assuntos
Educação Médica Continuada/métodos , Laparoscopia/educação , Comunicação por Videoconferência , China , Humanos , Japão , Controle de Qualidade , Fatores de Tempo
14.
Dig Dis Sci ; 58(12): 3503-15, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23979441

RESUMO

BACKGROUND: Intratumoral hypoxia and epithelial-mesenchymal transition are involved in tumor invasion and metastasis. AIMS: This study investigated the molecular mechanisms that relay the hypoxia signal into the epithelial-mesenchymal transition and metastasis. METHODS: Morphology analysis and tumor cell migration and invasion assays were performed to detect phenotypic changes of pancreatic cancer cells under normoxic and hypoxic conditions after lentiviral HIF-1α shRNA transfection. Quantitative reverse transcription polymerase chain reaction, western blot, and immunohistochemistry were used to detect gene expression in pancreatic cancer cell lines and tissues or normal pancreatic tissues. Luciferase, gel shift, and ChIP assays were used to assess gene regulation. RESULTS: Under hypoxic conditions, these tumor cells underwent typical morphological and molecular changes to epithelial-mesenchymal transition. Moreover, Snail expression was induced by hypoxic conditions and was regulated by HIF-1α expression at the transcriptional level through HIF-1α-binding to the second site of hypoxia-responsive elements of the Snail gene promoter. In addition, Snail expression was associated with HIF-1α expression in pancreatic cancer tissues, and expression of both was associated with tumor metastasis and poor patient survival. CONCLUSIONS: Our study provides key evidence that HIF-1α and Snail are responsible for hypoxia-induced metastasis phenotypes in pancreatic cancer and that HIF-1α and Snail expression can be used as biomarkers to predict tumor metastasis and patient survival.


Assuntos
Carcinoma/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Hipóxia/metabolismo , Neoplasias Pancreáticas/metabolismo , Fatores de Transcrição/genética , Biomarcadores Tumorais/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Fatores de Transcrição da Família Snail , Fatores de Transcrição/biossíntese
15.
Clin Invest Med ; 35(4): E158-64, 2012 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-22863553

RESUMO

Endoscopic submucosal dissection (ESD) has been applied to, and gradually standardized for, early gastric cancers; however, it has not yet been widely used for treatment of colorectal neoplasms. Compared with gastric ESD, the thinner colorectal wall and winding nature of the colon make colorectal ESD a much more difficult operative technique. Despite greater risks of postoperative complications, particularly perforation of the colon, more and more endoscopists are making an effort to study this new technique in terms of its capability of larger neoplastic resection, higher en bloc resection rate and lower local recurrence rate of neoplasms in comparison with other endoscopic treatments. Thus, colorectal ESD may become the standard treatment for early colorectal neoplasms in the future. This review article discusses the current research on endoscopic submucosal dissection for colorectal neoplasms. Please see supplementary files for the accompanying video ESD with snare.


Assuntos
Colo/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Colo/patologia , Neoplasias Colorretais/patologia , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
16.
World J Gastroenterol ; 17(39): 4382-8, 2011 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-22110263

RESUMO

Although in the past two decades, laparoscopic surgery, considered as a great revolution in the minimally invasive surgery field, has undergone major development worldwide, another dramatic surgical revolution has quietly appeared in recent years. Ever since Kalloo's first report on transgastric peritoneoscopy in a porcine model in 2004, interest in a new surgical procedure named natural orifice transluminal endoscopic surgery (NOTES) has blossomed worldwide. Considering that a NOTES procedure could theoretically avoid any abdominal incision, operation-related pain and scarring, many surgeons and endoscopists have been enthusiastic in their study of this new technique. In recent years, several NOTES studies have been carried out on porcine models and even on humans, including transvaginal cholecystectomy, transgastric appendectomy, transvaginal appendectomy, and transvesical peritoneoscopy. So what is the current situation of NOTES and how many challenges do we still face? This review discusses the current research progress in NOTES.


Assuntos
Cirurgia Endoscópica por Orifício Natural/métodos , Animais , Humanos , Cirurgia Endoscópica por Orifício Natural/instrumentação
17.
PLoS One ; 6(10): e25941, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21991388

RESUMO

AIMS: Transducer and activator of transcription-3 (STAT3) plays an important role in tumor cell invasion and metastasis. The aim of the present study was to investigate the effects of STAT3 knockdown in nude mouse xenografts of pancreatic cancer cells and underlying gene expression. METHODS: A STAT3 shRNA lentiviral vector was constructed and infected into SW1990 cells. qRT-PCR and western immunoblot were performed to detect gene expression. Nude mouse xenograft assays were used to assess changes in phenotypes of these stable cells in vivo. HE staining was utilized to evaluate tumor cell invasion and immunohistochemistry was performed to analyze gene expression. RESULTS: STAT3 shRNA successfully silenced expression of STAT3 mRNA and protein in SW1990 cells compared to control cells. Growth rate of the STAT3-silenced tumor cells in nude mice was significantly reduced compared to in the control vector tumors and parental cells-generated tumors. Tumor invasion into the vessel and muscle were also suppressed in the STAT3-silenced tumors compared to controls. Collagen IV expression was complete and continuous surrounding the tumors of STAT3-silenced SW1990 cells, whereas collagen IV expression was incomplete and discontinuous surrounding the control tumors. Moreover, microvessel density was significantly lower in STAT3-silenced tumors than parental or control tumors of SW1990 cells. In addition, MMP-7 expression was reduced in STAT3-silenced tumors compared to parental SW1990 xenografts and controls. In contrast, expression of IL-1ß and IgT7α was not altered. CONCLUSION: These data clearly demonstrate that STAT3 plays an important role in regulation of tumor growth, invasion, and angiogenesis, which could be act by reducing MMP-7 expression in pancreatic cancer cells.


Assuntos
Técnicas de Silenciamento de Genes , Metaloproteinase 7 da Matriz/metabolismo , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/patologia , Fator de Transcrição STAT3/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células , Colágeno Tipo IV/metabolismo , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Imuno-Histoquímica , Masculino , Metaloproteinase 7 da Matriz/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microvasos/metabolismo , Microvasos/patologia , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
18.
World J Gastroenterol ; 17(25): 2992-3001, 2011 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-21799645

RESUMO

AIM: To evaluate the effect of RNA interference (RNAi) mediated silence of signal transduction and activation of transcription (STAT)3 on the growth of human pancreatic cancer cells both in vitro and in vivo. METHODS: STAT3 specific shRNA was used to silence the expression of STAT3 in pancreatic cancer cell line SW1990. The anti-growth effects of RNAi against STAT3 were studied in vitro and in experimental cancer xenografts in nude mice. The potential pathways involved in STAT3 signaling were detected using reverse transcription polymerase chain reaction and western blotting. RESULTS: The expression of the STAT3 was inhibited using RNAi in SW1990 cells. RNAi against STAT3 inhibited cell proliferation, induced cell apoptosis and significantly reduced the levels of CyclinD1 and Bcl-xL when compared with parental and control vector-transfected cells. In vivo experiments showed that RNAi against STAT3 inhibited the tumorigenicity of SW1990 cells and significantly suppressed tumor growth when it was directly injected into tumors. CONCLUSION: STAT3 signaling pathway plays an important role in the progression of pancreatic cancer, and silence of STAT3 gene using RNAi technique may be a novel therapeutic option for treatment of pancreatic cancer.


Assuntos
Vetores Genéticos/genética , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/genética , Ciclina D1/metabolismo , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Pancreáticas/genética , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/fisiologia , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
19.
Int J Oncol ; 38(6): 1637-44, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21479358

RESUMO

Signal transducers and activators of transcription 3 (STAT3) is a central cytoplasmic transcription factor that is activated by phosphorylation in response to extracellular signals and oncogenes. STAT3 regulates a number of pathways important in tumorigenesis including cell cycle progression, apoptosis, tumor angiogenesis, invasion and metastasis, and tumor cell evasion of the immune system. Our studies demonstrated that constitutively activated STAT3 plays an important role in the angiogenesis of pancreatic cancer. The objective of this study was to evaluate the potential use of RNA interference (RNAi) to knock down the STAT3 gene and the effect on angiogenesis of human pancreatic cancer cells in vitro and in vivo. We stably inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3) using RNAi in the SW1990 pancreatic cancer cell line. Furthermore, RNAi for STAT3 inhibited STAT3-induced HUVEC cell migration and cell proliferation, and significantly suppressed the levels of secreted vascular endothelial growth factor (VEGF) and matrix metalloproteinases-2 (MMP-2) of SW1990 cells. In vivo experiments showed that RNAi for STAT3 significantly suppressed tumor growth and angiogenesis of SW1990 cells. Furthermore, silencing the STAT3 gene in SW1990 cells by RNAi also led to a decrease of VEGF and MMP-2 at the mRNA and protein levels. Collectively, these results demonstrate that the STAT3 signaling pathway plays an important role in the angiogenesis of pancreatic cancer and that knockdown of the STAT3 gene using the RNAi technique may be a novel therapeutic option for the treatment of pancreatic cancer.


Assuntos
Neovascularização Patológica/patologia , Neoplasias Pancreáticas/fisiopatologia , Interferência de RNA , Fator de Transcrição STAT3/metabolismo , Animais , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Embrião de Galinha , Células Endoteliais/metabolismo , Inativação Gênica , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator de Transcrição STAT3/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Dig Dis Sci ; 56(4): 1090-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20927591

RESUMO

BACKGROUND: CD151, c-Met, and integrin alpha3/alpha6 are all involved in the hepatocyte growth factor (HGF)/c-Met signal pathway, which plays an important role in the malignant progression of tumors. AIMS: The purpose of this study was to explore the expression and prognostic significance of these proteins in pancreatic ductal adenocarcinoma (PDAC). METHODS: We used immunohistochemical methods to investigate the expression patterns of CD151, c-Met, and integrin alpha3/alpha6proteins in 71 patients with PDAC and in ten samples of normal pancreatic tissue. We also assessed correlations between these proteins and clinicopathological parameters and survival of PDAC patients using various statistical methods. RESULTS: CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in PDAC. CD151 and c-Met overexpressions were significantly associated with TNM stage (p=0.001 and p=0.038, respectively) and lymph node invasion (p=0.000, p=0.012, respectively). A significant positive linear correlation was found between CD151 and c-Met (r=0.583; p=0.000), integrin alpha3 (r=0.457; p=0.000), and integrin alpha6 (r=0.671; p=0.000). Overexpression of CD151, c-Met, integrin alpha3, or integrin alpha6 was related to poor survival of PDAC patients (p=0.000, p=0.000, p=0.005, and p=0.003, respectively), and CD151 and c-Met were independent factors in prognosis of PDAC. CONCLUSIONS: CD151, c-Met, and integrin alpha3/alpha6 were all overexpressed in PDAC. CD151 and c-Met might be new molecular markers to predict the prognosis of PDAC patients.


Assuntos
Antígenos CD/biossíntese , Carcinoma Ductal Pancreático/diagnóstico , Integrina alfa3/biossíntese , Integrina alfa6/biossíntese , Neoplasias Pancreáticas/diagnóstico , Proteínas Proto-Oncogênicas c-met/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Tetraspanina 24
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