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1.
Opt Express ; 31(24): 40907-40915, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041379

RESUMO

In this paper, what we believe to be a novel method is proposed to suppress the fading effect of the phase-sensitive optical time domain reflectometer (Ф-OTDR) by using a phase-modulated optical frequency comb. In the Ф-OTDR system, intensity distributions of Rayleigh backscattering (RBS) light are different for pulsed probe lights with different central frequencies, therefore the locations of the fading points corresponding to signals of different frequencies are differently distributed, allowing the use of frequency division multiplexing to suppress the fading effects. In the experimental system of this paper, a continuous light in the form of a frequency comb is firstly generated through phase modulation. It is then modulated into a pulsed probe light and injected into the sensing fiber to produce different RBS intensity distributions. Finally, the extracted phase is processed by using the amplitude evaluation method, so that the distorted phase can be eliminated. Fading suppression is achieved using our system, and the effect of suppression is evaluated. By using an equal-amplitude optical frequency comb containing seven frequency components, the fading probability density of the system is dramatically reduced from the range of 5.49%-9.83% to 0.08%. Compared with the conventional system using a single acoustic-optic modulator to generate the frequency shift, the method proposed in this paper features a larger modulation bandwidth and more flexible frequency combination scheme to better suppress the fading effect. This method does not sacrifice the response bandwidth of the system, and the phase delay can be precisely controlled, which helps to fully suppress the fading effect.

2.
World J Surg Oncol ; 21(1): 1, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36588150

RESUMO

BACKGROUND: Self-expanding metal stents (SEMS) served as a bridge to surgery (BTS). However, this method may be associated with worse long-term prognosis and relapse of CRC patients. Therefore, we attempted to clarify this in the angle of circulating tumor cells (CTCs). METHODS: A multicenter study was performed from March 2018 to January 2021. Thirty-two colorectal cancer patients with obstruction were selected, of which 21 patients were performed SEMS as a BTS while 11 patients were performed emergency surgery. Bloods samples were collected in two groups of patients for further detecting CTCs. In the SEMS group, the samples were collected before and after stent insert and after radical surgery performed. In the ES group, the samples were collected before stent insert and after emergency surgery performed. RESULTS: The number of CTCs did not show statistically significant differences before and after stent placement (34.90 vs 38.33, p=0.90), neither between the SEMS group and ES group in initial CTC levels (34.90 vs 58.09, p=0.394). No significant differences (38.33 vs 58.09, p=0.632) were observed after stent insert in the SMES group and the initial CTC levels in the ES group. Moreover, no major differences (24.17 vs 42.27, p=0.225) were observed after radical operation performed in both groups. CONCLUSION: The treatment of SEMS does not cause an increase in the number of CTC after stent insertion. Furthermore, there are may be other factors besides CTC to cause these poorer oncologic outcomes after SEMS placement.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Células Neoplásicas Circulantes , Stents Metálicos Autoexpansíveis , Humanos , Stents Metálicos Autoexpansíveis/efeitos adversos , Recidiva Local de Neoplasia/complicações , Colo/patologia , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Obstrução Intestinal/patologia , Stents/efeitos adversos , Resultado do Tratamento , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Estudos Retrospectivos
3.
Sensors (Basel) ; 22(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684638

RESUMO

An all-fiber distributed airflow sensing method based on a differential pulse-width pair Brillouin optical time domain analysis (DPP-BOTDA) and a self-heated high-attenuation fiber (HAF) is proposed and demonstrated. The HAF heated the sensing fiber, producing a gradient temperature distribution in it through physical contact, where the temperature distribution was obtained by DPP-BOTDA with a spatial resolution of 5 cm. The heat loss caused by the airflow was reflected in the decrease in the Brillouin frequency shift and spatially resolved by DPP-BOTDA. Distributed airflow sensing was experimentally demonstrated for measurements of airflow movement, multiple airflow sources and the deflection angle of the airflow. The positioning error of the airflow was no larger than ~2.2 cm; for the deflection angle measurements of the airflow, the maximum demodulation error was 2.5° within the angle range of 0-30°.

4.
Int J Nanomedicine ; 16: 6889-6904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675513

RESUMO

INTRODUCTION: Excessive production of reactive oxygen species (ROS) to induce high oxidative stress is one of the main causes of colitis; thus, it has been regarded as a therapeutic target for colitis treatment. And the nanomaterial-based therapeutic strategies are effective against colitis. However, the previous elaborately designed materials exhibit limited application due to the uncertain biocompatibility and complicated manufacturing processes. METHODS: In this study, the highly monodisperse hollow CeO2 nanoparticles (H-CeO2) with uniform morphology were obtained by in situ growing CeO2 on solid silica nanoparticles and subsequently removing the silica core. The H-CeO2 was further modified with PEG, which owned excellent biological stability and biocompatibility. The experimental model of colitis induced by dextran sulfate sodium (DSS) was used to investigate the anti-inflammatory effect of H-CeO2-PEG. RESULTS: The H-CeO2-PEG showed good ROS scavenging efficacy and decreased the levels of proinflammatory cytokines (IL-6, IL-1ß, IL-18, and TNF-α) in DSS-induced colitis mice. Furthermore, H-CeO2-PEG inhibited the activation of the MAPK signalling pathway to alleviate colitis. CONCLUSION: This study reveals the therapeutic effects of CeO2-based nanomedicine toward colitis and elucidates the specific signalling pathway involved, which provides potential alternative therapeutic options for patients with inflammation tissue.


Assuntos
Colite , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana , Humanos , Inflamação , Camundongos , Estresse Oxidativo , Espécies Reativas de Oxigênio
5.
Front Cell Dev Biol ; 9: 662707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277610

RESUMO

BACKGROUND: Gastric cancer is associated with tumor microenvironment and chronic inflammation, but the underlying tumor-promoting mechanisms still remain unknown. METHODS: The ATAC-seq was used to identify genes with chromatin accessibilities in promoter regions. The RNA-seq datasets were performed to identify differentially expressed genes (DEGs). Pearson correlation analysis with the mRNA expression of three families of tumor-related inflammation TFs was used to filter downstream DEGs. Cox univariate survival analysis was performed to identify the prognostic value. The ImmPort database and CIBERSORTx algorithm were used to investigate the regulatory relationship between hub DEGs and immune cells. Immunohistochemistry (IHC) and multidimensional database were performed to verification. RESULTS: In this case, we require 2,454 genes with chromatin accessibility in promoter regions by ATAC-seq. Based on the gene expression profiles (RNA-seq), we identified 365 genes with chromatin accessibility and differential expression. Combined with the Cox univariate survival analysis, we identified 32 survival-related DEGs with chromatin accessibility. According to ImmPort database, CXCL3, PLXNC1, and EDN2 were identified as immune- related genes in STAD. By applying the CIBERSORTx algorithm and Pearson correlation, PLXNC1 was the only gene correlated with various immune cells, significantly associated with M2 macrophages. Furthermore, gene set variation analysis (GSVA) suggests the "hallmark_interferon_gamma_response" pathway was most significantly correlated with PLXNC1. Immunohistochemistry results revealed that PLXNC1 protein level was significantly higher in STAD tissues than in normal tissues (p < 0.001). CONCLUSION: PLXNC1, regulated by IRF5, is an immune-related gene that was significantly associated with M2 macrophages and poor outcome in stomach adenocarcinoma.

6.
Oncol Lett ; 21(6): 480, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33968196

RESUMO

[This corrects the article DOI: 10.3892/ol.2021.12474.].

7.
BMC Surg ; 21(1): 148, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743658

RESUMO

BACKGROUND: Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. METHODS: A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. RESULTS: Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052-5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053-1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116-2.607), p = 0.014) were positively correlated with overall survival in matched patients. CONCLUSIONS: Self-expanding metal stents as "a bridge to surgery" are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.


Assuntos
Doenças do Colo , Tratamento de Emergência , Obstrução Intestinal , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Colo/cirurgia , Doenças do Colo/terapia , Feminino , Humanos , Obstrução Intestinal/cirurgia , Obstrução Intestinal/terapia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Resultado do Tratamento
8.
Oncol Lett ; 21(3): 213, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33510814

RESUMO

Chalcones and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. However, the in vivo anticancer effects and associated mechanisms of chalcones against intestinal tumorigenesis currently remain unclear. The aim of the present study was to investigate the chemopreventive effect of a chalcone derivative, 4'-hydroxychalcone (4-HC), in a transgenic adenomatous polyposis coli multiple intestinal neoplasia mouse model (ApcMin) of spontaneous intestinal adenomas. ApcMin mice were fed 4-HC (10 mg/kg/day) or the vehicle control by oral gavage starting at 8 weeks of age, and were sacrificed at 20 weeks. The administration of 4-HC significantly decreased the number of colon adenomas by 45% and the size of colon adenomas by 35% compared with the respective controls. Similarly, the number of adenomas in the distal small intestine (DSI) and proximal small intestine also decreased by 35 and 33%, respectively, in 4-HC-treated mice, and adenoma size in the DSI decreased by 39% compared with the respective controls. Treatment with 4-HC strongly decreased proliferation in colon and DSI adenomas, as detected by immunofluorescence staining with the proliferation marker protein Ki-67, and promoted apoptosis in colon adenomas, as detected by TUNEL immunofluorescence staining. In addition, decreased mRNA expression of ß-catenin target genes, including c-Myc, Axin2 and CD44, in colon adenomas of 4-HC-treated animals demonstrated the involvement of the Wnt/ß-catenin signaling pathway in the initiation and progression of colon neoplasms. Treatment with 4-HC also decreased the protein levels of ß-catenin in colon adenomas, as demonstrated by immunofluorescence staining. The results suggested that 4-HC may be a promising candidate for the chemoprevention of intestinal tumorigenesis, and further investigations are required to evaluate its clinical utility.

9.
Arch Med Sci ; 15(4): 979-991, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31360192

RESUMO

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies. However, the molecular mechanisms underlying PDAC are still not completely understood. Circular RNAs (circRNAs) are a unique class of RNA formed by special loop splicing. More and more researchers have paid attention to circRNAs. MATERIAL AND METHODS: In this study, we constructed a circRNA-mediated competing endogenous RNA (ceRNA) network in PDAC. Gene ontology (GO) analysis was performed to explore circRNAs' potential roles in PDAC progression. We also constructed an up-stream transcriptional network of circRNAs' parental genes and found that many transcription factors (TFs), such as tumor protein p53 (TP53) and MYC, could regulate their expression. RESULTS: This study, which aimed to identify differentially expressed circRNAs in PDAC, suggested that circRNAs may also act as biomarkers for PDAC. We analyzed two public datasets (GSE69362 and GSE79634) to identify differentially expressed circRNAs in PDAC. Finally, we found that DExH-Box Helicase 9 (DHX9) may be a potential regulator of circRNA formation in PDAC. Genomic loci of four down-regulated circRNAs - hsa_circ_000691, hsa_circ_0049392, hsa_circ_0005203, and hsa_circ_0001626 - contained DHX9 binding sites, suggesting that they may be directly regulated by DHX9. CONCLUSIONS: Our study identified differentially expressed circRNAs in PDAC, suggesting that circRNAs may also act as biomarkers for PDAC. Additional investigations of function and up-stream regulation of differentially expressed circRNA in PDAC are still needed.

10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(12): 1375-1380, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29280120

RESUMO

OBJECTIVE: To investigate the clinical effect of the application of "compound anastomotic device" on the high-risk colorectal anastomosis in rectal cancer patients undergoing protective ileostomy. METHODS: A total of 116 rectal cancer patients undergoing surgical procedure and prophylactic ileostomy in Tongji Hospital (90 cases) and The Third People's Hospital of Jingdezhen City (26 cases) from May 2011 to October 2016 were prospectively enrolled in the study. Paralleled control study and random digital table were applied. Fifty-eight cases received the compound anastomotic device for protective ileostomy (anastomosis ring group) and 58 cases underwent traditional terminal ileostomy (traditional group). The compound device was mainly composed of Valtrac biodegradable anastomosis ring, drainage tube and condom. Operational procedure was as follows: Ileocecum was freed through incision following laparoscopic total mesorectal excision; Two intestinal ring-shape purses were made; Intestinal wall between purse string was cut and the compound anastomotic device was put into; The purse was tightened and anastomosis ring was closed; The compound device was embed and pull out through the Trocar hole in the right lower abdomen; Then the drainage tube was fixed to the abdominal wall and connected with a drainage bag or an outer pocket. Incidence of anastomotic leak, stoma-related complications, hospital stay and total cost of two groups were compared. RESULTS: The general clinical data between two groups were not significantly different(all P>0.05). Stoma operation was performed successfully in all the patients of two groups. The stoma operation time was (34.6±13.8) min in anastomosis ring group and (25.8±14.0) min in traditional group with significant difference (t=2.123, P=0.035). Postoperative anastomotic leak occurred in 7 cases, including 3 cases with small fistula in traditional group and 4 cases in anastomosis ring group, of whom 1 case underwent left-low abdominal colonic stoma after necrotic intestine resection. All the patients were discharged within postoperative 7 to 37 days. In traditional group, 35 cases (60.3%) occurred stoma-related complications, the total hospitalization expenses was (65±28) thousand yuan, and the average hospital stay (including stoma reversion) was (23.6±11.8) days. In anastomosis ring group, 17 cases (29.3%) occurred stoma-related complications, the total hospitalization expense was (52±11) thousand Yuan, and the average hospital stay was (21.0±16.8) days. The incidence of anastomotic fistula and the hospital stay had no significant difference between two groups (all P>0.05). The stoma-related complication morbidity (χ2=3.216, P=0.002) and the total hospitalization expenses (t=2.683, P=0.027) in anastomosis ring group were significantly lower than those in traditional group. CONCLUSION: Compared with traditional ileostomy, the application of compound anastomotic device for protective ileostomy would be better to benefit the recovery of patients.


Assuntos
Anastomose Cirúrgica , Ileostomia , Neoplasias Retais/cirurgia , Fístula Anastomótica , Humanos , Complicações Pós-Operatórias , Reto , Estudos Retrospectivos
11.
Exp Mol Med ; 49(11): e399, 2017 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-29170478

RESUMO

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas Imediatamente Precoces/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Expressão Gênica , Humanos , Proteínas Imediatamente Precoces/genética , Proteínas Imediatamente Precoces/metabolismo , Masculino , Camundongos , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Mol Ther Nucleic Acids ; 8: 36-45, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28918036

RESUMO

The mutated in colorectal cancer (MCC) gene is an important colorectal tumor suppressor gene, although few studies have reported the microRNA(s) that could directly target MCC in colorectal cancer. Here, we used microRNA (miRNA) target prediction algorithms, and previously reported microarray data in human colorectal cancer found that only miR-4261 was predicted by all three databases to directly target MCC. Based on specimens from our own cohort of colorectal cancer patients, we further demonstrated that miR-4261 was overexpressed in colorectal cancer. Interestingly, overexpression of miR-4261 could enhance cell proliferation and G1/S phase transition of cell cycle, and promote cell migration in HCT116 and HT29 cells, while inhibition of miR-4261 had opposite effects. Luciferase reporter assay and western blot analysis confirmed MCC as a direct target of miR-4261. MCC small interfering RNA (siRNA) could abolish the suppressive effects of miR-4261 inhibitor on cell proliferation and migration in HCT116 and HT29 cell lines. Finally, we showed that therapeutic intervention with lentivirus-based miR-4261 sponge injection could effectively reduce tumor growth and inhibit cell proliferation in colorectal cancer xenograft. Collectively, our study is the first one to unravel the functional role of miR-4261, and it provides strong evidence that inhibition of miR-4261 through targeting of MCC might exert a therapeutic effect for colorectal cancer.

13.
Int J Med Sci ; 14(10): 937-942, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28924364

RESUMO

Background: Better understanding the molecular mechanisms responsible for the genesis and progression of colorectal cancer would help advance the novel therapeutics. miR-224 has been identified to be elevated in colorectal cancer and promote human colorectal cancer cell line SW480 proliferation and invasion. However, the effect of miRNAs on cancer cell proliferation could be significantly changeable among different cell lines. HCT116 is a commonly used cell line for colorectal cancer study and the target gene responsible for the function of miR-224 in its proliferation is unclear. Methods: miR-224 expression was determined by quantitative reverse transcription polymerase chain reactions (PCRs) in human colorectal cancer tissues compared with their corresponding matched peritumoral tissues. HCT116 cell viability and cell proliferation were determined by CCK-8, EdU incorporation assays and flow cytometry for cell cycle. Target gene of miR-224 was confirmed by Western blots and siRNA for Smad4. Results: miR-224 was significantly increased by 29.49 fold in colorectal cancer tissues compared with their corresponding matched peritumoral tissues based on 12 colorectal cancer patients. miR-224 mimic significantly increased HCT116 cell viability, EdU positive cells rate, and decreased G1 phase cell population and increased S phase cell population. miR-224 inhibitor had opposite effects. Smad4 could be negatively regulated by miR-224 in HCT116 cells and was responsible for its effects in proliferation. Conclusion: miR-224 mediates HCT116 cell proliferation by targeting Smad4.


Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Proteína Smad4/genética , Movimento Celular , Proliferação de Células/genética , Sobrevivência Celular/genética , Citometria de Fluxo , Fase G1/genética , Células HCT116 , Humanos , MicroRNAs/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Fase S/genética
14.
Adv Exp Med Biol ; 998: 271-281, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28936746

RESUMO

Despite years of researches, cardiovascular disease (CVD) remains the most common cause of death around the world. Lots of studies showed that by pretreating with short nonfatal ischemia in in situ organ or distant organ, one could develop tolerance to the following fatal ischemia. The process is called ischemic preconditioning (IPC). IPC prepare the heart for damage by producing inflammatory signals, miRNA, neuro system stimulation and exosomes. Among them, exosomes have been gaining increasing interest since it is characterized by its capability to carry information and its specific ligand-receptor system. Here we will discuss IPC induced exosomes and its protective effects during ischemic heart disease.


Assuntos
Exossomos/transplante , Precondicionamento Isquêmico Miocárdico/métodos , Infarto do Miocárdio/cirurgia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Oxigênio/metabolismo , Transplante de Células-Tronco , Animais , Hipóxia Celular , Exossomos/metabolismo , Exossomos/patologia , Humanos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Recuperação de Função Fisiológica , Regeneração
15.
J Cancer ; 8(12): 2256-2262, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28819428

RESUMO

Colorectal cancer (CRC) is one of the most leading causes of cancer-related death worldwide. The serum and glucocorticoid inducible kinase SGK1 is highly expressed and involved in several tumors. GSK650394, a SGK1 inhibitor, has been proved to be effective in impeding tumor growth in vitro. In this study, we developed a novel analog of GSK650394, and evaluated its effects on CRC cells and tumor growth both in vitro and in vivo. HCT116 cells were treated with a concentration gradient of new developed compounds and cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 value of every analog. Cell proliferation analysis was estimated from EdU staining and flow cytometry in vitro, and immunohistochemistry of Ki67 and PCNA in vivo. Cell migration analysis was examined using the transwell assay. In vivo tumor growth was determined in athymic nude mice by injecting the HCT116 cells in the subcutaneous tissue, followed by the injection of QGY-5-114-A. We found that new developed GSK650394 analog QGY-5-114-A has lower IC50 value, and treatment with QGY-5-114-A significantly inhibited CRC cell proliferation and migration in vitro. Besides that, colonic tumor growth was also dramatically restricted by QGY-5-114-A in vivo. In conclusion, pharmacological treatment with QGY-5-114-A impedes CRC tumor cell proliferation, migration and tumor growth.

16.
Theranostics ; 7(7): 1901-1913, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28638476

RESUMO

Dysregulation of microRNAs (miRNAs, miRs) and their putative target genes have been increasingly reported to contribute to colorectal cancer. However, miRNAs that directly target the mutated in colorectal cancer (MCC) gene, a tumor suppressor which is downregulated or inactivated in colorectal cancer, remain largely unknown. By using an array-based miRNA analysis, we identified a group of miRNAs that were dysregulated in human metastatic versus non-metastatic colorectal cancer tissues. One of these miRNAs, miR-4260, was predicted to target MCC in the miRDB database. Results using human HCT116 and HT29 colorectal cancer cell lines showed that miR-4260 mimic enhanced cell proliferation and migration and reduced apoptosis induced by the chemotherapeutic agent 5-fluorouracil while miR-4260 inhibitor had inverse effects. Furthermore, miR-4260 negatively regulated MCC as well as SMAD4 by directly binding to the 3'untranslational region (3'UTR). Using siRNAs targeting MCC or SMAD4, we showed that upregulation of MCC and SMAD4 was essential to mediate the functional roles of miR-4260 inhibitor in colorectal cancer cells. Our in vivo experiments indicated that inhibition of miR-4260 reduced colorectal tumor growth in nude mice subcutaneously implanted with HCT116 cells. Significantly, miR-4260 was increased in human colorectal cancer tissues with simultaneous downregulation of MCC and SMAD4, strongly suggesting the clinical relevance of targeting miR-4260 in the treatment of colorectal cancer. In summary, we identified miR-4260 as a novel oncomiR for colorectal cancer that targets MCC and SMAD4. Inhibition of miR-4260 can, therefore, be a potential therapeutic strategy for colorectal cancer.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Proteína Smad4/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Apoptose , Produtos Biológicos/administração & dosagem , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/patologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Camundongos Nus , Análise em Microsséries , Transplante Heterólogo , Resultado do Tratamento
17.
Scand J Gastroenterol ; 51(1): 8-15, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26228994

RESUMO

BACKGROUND: Reporting of surgical complications is common, but few provide information about the severity and estimate risk factors of complications. If have, but lack of specificity. METHODS: We retrospectively analyzed data on 2795 gastric cancer patients underwent surgical procedure at the Affiliated Hospital of Qingdao University between June 2007 and June 2012, established multivariate logistic regression model to predictive risk factors related to the postoperative complications according to the Clavien-Dindo classification system. RESULTS: Twenty-four out of 86 variables were identified statistically significant in univariate logistic regression analysis, 11 significant variables entered multivariate analysis were employed to produce the risk model. Liver cirrhosis, diabetes mellitus, Child classification, invasion of neighboring organs, combined resection, introperative transfusion, Billroth II anastomosis of reconstruction, malnutrition, surgical volume of surgeons, operating time and age were independent risk factors for postoperative complications after gastrectomy. Based on logistic regression equation, p=Exp∑BiXi / (1+Exp∑BiXi), multivariate logistic regression predictive model that calculated the risk of postoperative morbidity was developed, p = 1/(1 + e((4.810-1.287X1-0.504X2-0.500X3-0.474X4-0.405X5-0.318X6-0.316X7-0.305X8-0.278X9-0.255X10-0.138X11))). The accuracy, sensitivity and specificity of the model to predict the postoperative complications were 86.7%, 76.2% and 88.6%, respectively. CONCLUSIONS: This risk model based on Clavien-Dindo grading severity of complications system and logistic regression analysis can predict severe morbidity specific to an individual patient's risk factors, estimate patients' risks and benefits of gastric surgery as an accurate decision-making tool and may serve as a template for the development of risk models for other surgical groups.


Assuntos
Gastrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Neoplasias Gástricas/cirurgia , Idoso , China , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
18.
Biomed Res Int ; 2016: 6241763, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28105427

RESUMO

The heart is recognized as an organ that is terminally differentiated by adulthood. However, during the process of human development, the heart is the first organ with function in the embryo and grows rapidly during the postnatal period. MicroRNAs (miRNAs, miRs), as regulators of gene expression, play important roles during the development of multiple systems. However, the role of miRNAs in postnatal heart growth is still unclear. In this study, by using qRT-PCR, we compared the expression of seven cardiac- or muscle-specific miRNAs that may be related to heart development in heart tissue from mice at postnatal days 0, 3, 8, and 14. Four miRNAs-miR-1a-3p, miR-133b-3p, miR-208b-3p, and miR-206-3p-were significantly decreased while miR-208a-3p was upregulated during the postnatal heart growth period. Based on these results, GeneSpring GX was used to predict potential downstream targets by performing a 3-way comparison of predictions from the miRWalk, PITA, and microRNAorg databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to identify potential functional annotations and signaling pathways related to postnatal heart growth. This study describes expression changes of cardiac- and muscle-specific miRNAs during postnatal heart growth and may provide new therapeutic targets for cardiovascular diseases.


Assuntos
Regulação da Expressão Gênica/fisiologia , Coração/crescimento & desenvolvimento , MicroRNAs/biossíntese , Animais , Feminino , Humanos , Masculino , Camundongos
19.
Medicine (Baltimore) ; 94(50): e2277, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26683954

RESUMO

To compare the clinical outcomes and prognoses in patients with gastroesophageal junction adenocarcinoma (Siewert type II/III), by transthoracic and transabdominal hiatal approaches. Siewert II/III gastroesophageal junction adenocarcinomas patients (334 cases) underwent different surgical procedures at the Affiliated Hospital of Qingdao University from July 2007 to July 2012 and were analyzed retrospectively. In total, 140 patients underwent surgery by the transthoracic approach, and 194 patients underwent the transabdominal hiatal approach mainly with radical total and proximal gastrectomy (D2). All patients were followed up by telephone review or by outpatient reexamination until July 2013. The surgically related and clinical outcomes were compared using the χ2 test, t test, Fisher exact test, or nonparametric rank sum test according to different data. The survival curve was drawn by the Kaplan-Meier method and survival analysis used Cox regression analysis. The operative time, length of resected esophagus, number of lymph nodes harvested, postoperative pain scores, postoperative hospital stay, time of antibiotics use, postoperative morbidity, and costs for the transabdominal surgery group were better than that of the transthoracic group. The overall 5-year survival rate was 35.3% and 40.3%, respectively, in the transthoracic and transabdominal surgery groups, and differences were not statistically significant (x2 = 2.311, P > 0.05). The hazard ratio of death for the transthoracic compared with the transabdominal approach was 1.27 (0.93-1.72, P > 0.05). According to tumor node metastasis (TNM) staging, stratification analysis showed that stage III patient overall survival rates were 25.7% and 37.2%, respectively. The differences were statistically significant (x2 = 4.127, P < 0.05). In uni- and multivariate Cox regression analysis, the hazard ratio for the transabdominal versus the transthoracic approach was 0.66 (0 43 to 0.99, P < 0.05) and 1.47 (1.05-2.06, P < 0.05), respectively. There were no significant differences of 5-year overall survival in TNM stage I and II of the Siewert II/III adenocarcinoma patients, but improved survival of TNM stage III patients undergoing transabdominal hiatal compared with transthoracic total radical and proximal gastrectomy. The short-term clinical outcomes improved with the transabdominal hiatial surgery group.


Assuntos
Adenocarcinoma/cirurgia , Junção Esofagogástrica , Gastrectomia/métodos , Hospitais de Ensino , Neoplasias Gástricas/cirurgia , Abdome , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tórax , Resultado do Tratamento
20.
J Surg Res ; 191(2): 413-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25060322

RESUMO

BACKGROUND: There is no consensus as to the impact of lymph node micrometastases (LNMM) on survival of patients with gastric cancer. The aim of this analysis was to investigate the prognostic significance of LNMM in patients with histologic node-negative gastric cancer. METHODS: We searched relevant studies from PubMed, Embase, and the Cochrane Library (1966-2013.5), used software STATA 12.0 to pool the outcomes of each study. Mantel-Haenszel and Inverse Variance methods were used in a fixed effect model and a random effect model, respectively. The hazard ratios (HR) and odds risk (OR) at their 95% confidence intervals (CIs) were used as measures to investigate the prognostic importance of LNMM, by searching for a correlation between the clinical pathologic features and LNMM. RESULTS: Our analysis of 18 eligible studies revealed that patients with LNMM had an increased likelihood of having a worse 5-y survival rate (HR 2.81; 95% CI: 1.96-4.02). Subgroup analyses showed a more significant result for patients in pT1-2N0 (HR 3.52; 95% CI 1.88-6.62). The analyses also revealed that (OR 1.32; 95% CI 1.17-1.48), lymphatic invasion (OR 2.21; 95% CI 1.42-3.44) and venous invasion (OR 1.41; 95% CI 1.08-1.85) were associated with the occurrence of LNMM. CONCLUSIONS: There is a positive correlation between LNMM and an unfavorable surgical outcome in gastric cancer. Undifferentiated histologic findings, lymphatic invasion, and venous invasion are high risk factors for the occurrence of LNMM.


Assuntos
Micrometástase de Neoplasia , Neoplasias Gástricas/patologia , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Estudos Observacionais como Assunto , Prognóstico , Viés de Publicação , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
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