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OBJECTIVE: This study employed a randomized controlled trial to assess the efficacy of virtual-reality (VR) simulators and physical model simulators on colonoscopy training to explore the optimal and evidence-based simulation training. DESIGN: Forty participants were divided into 2 groups and randomized as dyads: the VR simulator group and the physical model simulator group. All the participants performed a baseline test through porcine colonoscopy. After a 6 h simulation training, each participant underwent a post-test on a pig after bowel preparation, and the procedures were video-recorded. Both the baseline test and the post-test were blindly assessed by 2 experienced assistant director physicians based on the GAGES-C scoring system. SETTING: Simulation center, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai. PARTICIPANTS: Forty surgical residents without colonoscopy experience. RESULTS: Both the VR simulator group and the physical model simulator group improved significantly over the baseline test. The VR simulator group performed significantly better than the physical model simulator group, p=0.042. The participants in both groups expressed a high level of simulator satisfaction. CONCLUSIONS: Novice residents can benefit from both VR simulators and physical model simulators. The VR simulator was shown to be more effective for colonoscopy training. VR simulators were more recommended for novices conducting basic colonoscopy training.
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Competência Clínica , Colonoscopia , Internato e Residência , Treinamento por Simulação , Realidade Virtual , Colonoscopia/educação , Humanos , Treinamento por Simulação/métodos , Feminino , Masculino , Internato e Residência/métodos , Suínos , Adulto , Animais , Educação de Pós-Graduação em Medicina/métodos , ChinaRESUMO
This randomized controlled trial compared the efficacy of virtual-reality (VR) simulator training and surgical training on live pigs to explore the most effective and evidence-based training modality. Materials and methods: Thirty-six novice surgical residents without independent laparoscopic experience were randomly paired with a peer and randomized into three groups: VR simulator group (dyad training on LapSim VR simulators), pig surgery group (training on live, anesthetized pigs) and control group (training by a lecture on laparoscopic surgery, surgical videos and textbooks). After 6 h of training, all participants performed a simulated cholecystectomy procedure using a pig liver with adherent gallbladder working in pairs. All procedures were video-recorded and the recordings were saved on USB-sticks in a blinded fashion identifiable only by the unique participant number. All video-recordings were scored blindly and independently by two expert raters using the Global Operative Assessment of Laparoscopic Skills (GOALS) assessment instrument. Results: The performances in the three groups were significantly different, P less than 0.001. Both the VR simulation training group and the live pigs training group performed significantly better than the control group, both P values less than 0.001. However, there was no significant difference in the performance of the two simulation-based training groups, P=0.66. Conclusion: Novice surgical trainees can benefit from both VR simulator training and pig surgery simulation compared with traditional studying and there was no significant difference between the two modalities. The authors recommend that VR simulators should be used for basic training of laparoscopic skills and surgery on live animals should be reserved for higher-level surgical training.
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The fungal microbiota is an important component of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation. However, how fungi regulate inflammatory bowel disease (IBD) is poorly understood. This study found that intestinal fungi regulate immune responses in IBD. Antibiotic-mediated depletion of fungi facilitated the development of IBD. Fungi greatly enhanced oxidative phosphorylation (OXPHOS) by enhancing glutaminolysis. Mechanistically, we found that fungi could activate the dectin-1-Syk- NF-κB signaling pathway to promote the expression of key enzymes and transporters involved in glutaminolysis. In summary, our findings reveal that fungal interactions in the human gut could be a promising therapeutic target for IBD.
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Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Linfócitos T CD4-Positivos , Disbiose/microbiologia , Fungos , Doenças Inflamatórias Intestinais/microbiologia , MamíferosRESUMO
Blue light regulates biological function in various cells, such as proliferation, oxidative stress, and cell death. We employed blue light illumination on human umbilical vein endothelial cells utilizing a LED device at 453 nm wavelength and revealed a novel biphasic response on human umbilical vein endothelial cells (HUVECs). The results showed that low fluence blue light irradiation promoted the fundamental cell activities, including cell viability, migration and angiogenesis by activating the angiogenic pathways such as the VEGF signaling pathway. In contrast, high fluence illumination caused the opposite effect on those activities by upregulating pro-apoptotic signaling cascades like ferroptosis, necroptosis and the p53 signaling pathways. Our results provide an underlying insight into photobiomodulation by blue light and may help to implement potential treatment strategies for treating angiogenesis-dependent diseases.
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Obesity is a major epigenetic cause for colorectal cancer (CRC). Leptin is implicated in obesity-associated CRC, but the underlying mechanism remains unclear. The current study identified over-expression of metallopanstimulin-1 (MPS-1) in CRC patients through microarray and histological analysis, especially in obese CRC patients. MPS-1 was correlated with advanced tumor stage, suggesting its association with CRC progression. In addition, MPS-1 over-expression was associated with poor overall survival (OS) in obese CRC patients, but not in their non-obese counterparts, suggesting its potential as a prognostic marker of obese CRC patients. MPS-1 expression was positively associated with circulating leptin levels in CRC patients, especially in obese cases. Functional experiments demonstrated that MPS-1 silencing inhibited tumor proliferation and colony formation, and induced apoptosis of CRC cells in vitro. Converse results were obtained from the experiments with MPS-1 over-expression. Mechanistically, MPS-1 executed its action through induction of c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moreover, the promotion effect of MPS-1 on CRC progression was modulated by leptin. In vivo studies demonstrated that MPS-1 silencing suppressed tumor growth of CRC via inhibiting JNK/c-Jun signaling. Collectively, this study indicates that MPS-1 promotes leptin-induced CRC via activating JNK/c-Jun pathway. MPS-1 might represent a potent candidate for the treatment and prognostic prediction of obesity-associated CRC.
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Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Leptina/metabolismo , Metaloproteínas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas Ribossômicas/metabolismo , Transdução de Sinais , Células CACO-2 , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Humanos , MAP Quinase Quinase 4/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-jun/metabolismoRESUMO
BACKGROUND AND AIMS: Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, survival, apoptosis, and stem cell self-renewal. In addition, Hippo signalling is profoundly implicated in intestinal regeneration and cancer. However, its roles in the pathogenesis of Crohn's disease [CD] remain largely unexplored. METHODS: Quantitative reverse transcription-polymerase chain reaction [qRT-PCR] was performed to identify the deregulated molecules in Hippo signalling. Expression of the highly upregulated Yes-associated protein 1 [YAP] was subsequently examined by qRT-PCR, western blotting, and immunohistochemistry in the intestinal tissues of CD patients and the colons of 2,4,6-trinitrobenzene sulphonic acid [TNBS]-induced colitis mice. The microRNAs [miRNAs] predicted to target YAP were explored by transfection of miR-590-5p mimics or inhibitors and analyzed by luciferase reporter assay. The roles of the miR-590-5p/YAP axis in CD and colorectal cancer were studied in experimental colitis mice and colorectal cancer cell lines. RESULTS: YAP mRNA was significantly upregulated in intestinal epithelial cells in CD patients and TNBS-induced colitis mice. MiR-590-5p suppressed YAP expression by directly targeting the YAP 3'-untranslated region in Caco-2 cells and SW620 cells. Upregulation of miR-590-5p in colon reduced YAP level and its downstream targets in intestinal epithelial cells [IECs]. Treatment of miR-590-5p or YAP inhibitor Verteporfin alleviated experimental colitis. Targeting the miR-590-5p/YAP axis inhibited cell proliferation and invasiveness of colorectal cancer [CRC] cells in vitro. CONCLUSIONS: Our results suggest that miR-590-5p inhibits intestinal inflammation in mouse colon and tumourigenesis of colorectal cancer cells by inhibiting YAP. The miR-590-5p/YAP axis may be an important novel mechanism in the pathogenesis of CD and colorectal cancer.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Doença de Crohn/genética , Doença de Crohn/metabolismo , MicroRNAs/genética , Fosfoproteínas/genética , Regiões 3' não Traduzidas , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células CACO-2 , Proteínas de Ciclo Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Células Epiteliais/metabolismo , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Fosfoproteínas/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição , Transfecção , Regulação para Cima , Verteporfina/farmacologia , Proteínas de Sinalização YAPRESUMO
BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues. EETs were extracted from tissue homogenates and analyzed by liquid chromatography coupled with tandem mass spectrometry. RESULTS: The concentration of EETs was higher in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues (1.91⯱â¯0.98â¯ng/mg vs. 0.96⯱â¯0.77â¯ng/mg, mean⯱â¯SD, Pâ¯<â¯0.01). As shown by immunohistochemistry, sEH was present in the cytoplasm and intestinal mucosa and showed a decline in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues. Western blot analyses showed reduced sEH expression in ulcerative colitis tissues compared with matched adjacent non-inflamed tissues, whereas CYP2J2 increased in ulcerative colitis tissues (Pâ¯<â¯0.05). However, there was no statistically significant difference observed in CYP2C8 and CYP2C9 protein expression between them (Pâ¯>â¯0.05). CONCLUSION: Our data suggest that the increase in EET levels may be part of a protective mechanism in ulcerative colitis. Furthermore, the concentration of EETs could be a key factor for drug therapy for ulcerative colitis.
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Ácido 8,11,14-Eicosatrienoico/metabolismo , Colite Ulcerativa/metabolismo , Sistema Enzimático do Citocromo P-450/biossíntese , Epóxido Hidrolases/biossíntese , Regulação Enzimológica da Expressão Gênica , Adulto , Idoso , Colite Ulcerativa/patologia , Citocromo P-450 CYP2J2 , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Laparoscopic surgery is widespread and safe for the management of patients with colorectal cancer (CRC). Although the use of standard surgical techniques can prevent perioperative wound infections, surgical site infections (SSIs) remain an unresolved complication in laparoscopic-assisted colectomy. The present study investigated the ability of plastic wound protectors applied to the extraction incision during the externalized portion of the procedure to reduce the rate of infection in laparoscopic-assisted colectomy. We completed a retrospective review of the medical records of patients who underwent nonemergent laparoscopic-assisted between January 2015 and June 2016. Outcomes for patients with and without the use of a wound protector were compared. A total of 109 patients were included in this study. There was 1 patient in the wound protector group (nâ=â57) and 7 in the nonwound protector group (nâ=â52) who developed a wound infection at the colon extraction site (Pâ=â.02). Furthermore, the average postoperative hospital stay in the wound protector group was shorter compared to the nonwound protector group (7.47â±â0.24 vs 8.73â±â0.54 days, Pâ=â.03). In conclusion, this study indicates that the use of a plastic wound protector during laparoscope-assisted colectomy does reduce postoperative wound infection rates, and the wound protectors are beneficial for specimen extraction and digestive tract reconstruction.
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Colectomia/instrumentação , Neoplasias Colorretais/cirurgia , Laparoscopia/instrumentação , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Colectomia/métodos , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Plásticos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
The role of multidrug resistance associated protein 1 (MRP1) in the multidrug resistance (MDR) of colorectal cancer (CRC) remains unclear. The present study aimed to investigate the effect of MRP1 in MDR CRC and its therapeutic potential for the treatment of patients with this disease. The human MDR CRC cell lines HCT-8 and Colo205 were established through stable exposure to 5-florouracil (5-FU) over a 5-month period. MRP1 was knocked-down in MDR CRC cells through the transfection of short hairpin RNA targeting MRP1 (shMRP1). Western blotting was performed to assess the efficiency of this silencing. MTT and apoptosis assays were conducted to detect cell viability and apoptosis, respectively. Compared with their parental cells, HCT-8/5-FU and Colo205/5-FU cells were 23.1 and 15.8 times more resistant to 5-FU, and 17.2 and 20.9 times more resistant oxaliplatin, respectively. The knockdown of MRP1 resulted in the attenuation of the MDR phenotype through the induction of apoptosis. The shMRP1-transfected Colo205/5-FU cells were injected subcutaneously into the right scapular region of BALB/c nude mice and tumor size was measured for 15 days post-injection. This in vivo experiment demonstrated that MRP1 knockdown inhibited tumor growth. On the 9, 12 and 15th day post-injection, tumor volume in the shMRP1-transfected Colo205/5-FU cell-injected group was significantly lower compared with that in the Colo205/5-FU cell-injected group (day 9, 2.1±0.8 vs. 6.9±1.9 mm3, P=0.009; day 12, 3.1±1.4 vs. 14.3±4.0 mm3, P=0.008; day 15, 4.8±2.7 vs. 21.3±3.4 mm3; all P<0.001). These results demonstrate that MRP1 serves a role in the MDR phenotype of CRC through inhibiting apoptosis and may serve as a potential therapeutic target for inhibition, which would increase the efficacy of other chemotherapeutic agents in the treatment of CRC.
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Accumulating evidence suggests that aberrantly expressed microRNAs (miRNAs) contribute to the initiation and progression of human cancers. However, the underlying function of miR-193b in colorectal cancer (CRC) remains largely unexplored. Herein, we demonstrate that miR-193b is significantly down-regulated in CRC tissues compared with their normal counterparts. Kaplan-Meier analysis revealed that decreased miR-193b expression was closely associated with the shorter overall survival of patients with CRC. Through gain-and loss-of-function studies, we showed that miR-193b significantly suppressed CRC cell proliferation and invasion. In addition, bioinformatics analyses and luciferase reporter assays identified Stathmin 1 (STMN1) as the direct functional target of miR-193b in CRC. Furthermore, silencing of STMN1 resulted in a phenotype similar to that observed for overexpression of miR-193b, and restoration of STMN1 expression completely rescued the inhibitory effect of miR-193b in CRC cells. Taken together, our study implies the essential role of miR-193b in negatively regulating CRC progression, and a novel link between miR-193b and STMN1 in CRC.
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Odontogenic ameloblast-associated protein (ODAM), an acidic matricellular protein, has been implicated in several epithelial neoplasms. However, its biological functions and molecular mechanisms in cancer progression, particular colorectal carcinoma (CRC), remain unknown. Here we demonstrated that ODAM was significantly down-regulated in CRC tissues compared with their normal counterparts. Then, we established that ODAM expression level was closely correlated with CRC development and patient prognosis. The abnormal expression of ODAM dramatically affected CRC cell growth in vitro and in vivo. We further revealed that the inhibitory effects of ODAM on CRC cell growth were associated with PTEN elevation and PI3K/AKT signaling inactivation. Furthermore, we determined that silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing CRC cells. Our study suggests matricellular protein ODAM may serve as a novel prognostic marker and act as a CRC growth suppressor.
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Proteínas de Transporte/metabolismo , Proliferação de Células , Neoplasias Colorretais/enzimologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Idoso , Amiloide , Animais , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Estimativa de Kaplan-Meier , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas de Neoplasias , Transplante de Neoplasias , PTEN Fosfo-Hidrolase/genética , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Regulação para CimaRESUMO
OBJECTIVE: To investigate the efficacy of complete mesocolic excision (CME) in the radical operation for right hemicolon cancer. METHODS: Clinical data of 336 cases of right hemicolon cancer undergoing radical resection, including 218 cases of CME surgery group and 118 cases of traditional surgery group, from January 2005 to December 2014 in Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively analyzed. Intraoperational events, perioperative status and postoperative survival were compared between the two groups. RESULTS: The baseline information was not significantly different between the two groups (all P>0.05). The number of harvested lymph nodes in CME and traditional group was 11.4±0.3 and 9.3±0.5 respectively(P=0.000) and the proportion of greater than or equal to 12 lymph nodes per case was 47.3%(103/218) and 28.8%(34/118)(P=0.002), which both were significantly different. The operation time in CME and traditional group was (147.2±2.9) and (148.8±3.9) minutes, which was not significantly different (P>0.05), whereas operative blood loss was (125.7±7.5) and (305.1±20.5) milliliters in CME and traditional group with significant difference (P=0.000). Postoperative hospital stay was (12.9±0.9) and (16.3±1.0) days in CME and traditional group with significant difference (P=0.018), while the time to postoperative liquid intake and normal diet was not significantly different between two groups (both P>0.05). The morbidity of postoperative complication of CME group was lower compared to traditional group (14.2%, 31/218 vs. 24.6%, 29/118), which was significantly different (P=0.018). Among them, infection occurred in 19 (8.7%) cases and 21 (17.8%) cases with significant difference between the two groups (P=0.014). The average time of follow-up was (34.5±1.2) months and (27.9±1.5) months in CME and traditional group, and the five-year survival rate was 85.6% and 78.0% with significant difference(P=0.043). Moreover, 102 cases underwent laparoscopic-assisted CME and 116 cases underwent open CME in CME group. The 5-year survival rate was 89.8% and 82.2% in laparoscopic and open group with significant difference (P=0.048). CONCLUSION: Compared with traditional radical resection, CME radical resection for right hemicolon cancer can harvest more lymph nodes, decrease operative blood loss, lower the riskof postoperative complication, shorten the postoperative hospital stay, and increase the 5-year survival rate. Furthermore, laparoscopic-assisted CME has more advantages.
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Neoplasias do Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Excisão de Linfonodo , Mesocolo/cirurgia , Adulto , Perda Sanguínea Cirúrgica , Feminino , Humanos , Laparoscopia , Tempo de Internação , Linfonodos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The inducible T-cell co-stimulator (ICOS) belongs to the B7-CD28 immunoglobulin superfamily, which is currently the subject of intense study due to great successes gained in treatment of different malignancies by disrupting their family members. However, the role of ICOS played in colorectal cancer (CRC) remains poorly understood. A tissue microarray (n = 310) was stained with the ICOS specific antibody and ICOS expression is decreased in patients with either lymphatic or distant metastasis and inversely associated with CEA level and TNM stage of CRC patients. Importantly, high ICOS expression is significantly correlated with overall survival (OS) of CRC patients (n = 230, p < 0.001), and ICOS expression is also proved to be an independent prognostic factor by multivariate analysis. Surgical excised CRC specimens (n = 26) were enzymatically digested to get the tumor-infiltrating leukocytes and ICOS is mainly expressed on CD4(+) T cells and its ligand ICOSL is detected on macrophages and tumor cells. ICOS expression level is associated with increased cytotoxic T lymphocyte antigen (CTLA)-4 (p < 0.001) and programmed death (PD-1) (p = 0.005) expression on T cells and more infiltrated CD8(+) T cells (p < 0.001). Interestingly, ICOS(+)CD4(+) cells isolated from tumor tissues have high T-bet and interferon (IFN)γ expression, the characteristics of Th1 cells, compared to ICOS(-)CD4(+) cells. In addition, the correlation between the percentage of ICOS(+)CD4(+) T cells in tumor tissue and peripheral blood was detected. Conclusively, expression of ICOS is associated with improved survival in CRC and percentage of ICOS(+)CD4(+) cells acting as Th1 cells in either primary tumor tissue or peripheral blood may be a clinical biomarker for good prognosis of CRC patients.
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Aberrantly expressed microRNAs contribute to the initiation and progression of human cancers. However, the underlying functions of microRNA-187 (miR-187) in colorectal cancer (CRC) remain largely unexplored. Here, we demonstrated that miR-187 was significantly down-regulated in CRC tissues and cell lines compared to their normal counterparts. By Kaplan-Meier analysis, we revealed that decreased miR-187 expression was closely associated with shorter overall survival and relapse-free survival of patients with CRC. By gain- and loss-of-function studies, we showed that miR-187 remarkably suppressed CRC cell proliferation, migration, invasion, and promoted cell apoptosis. Furthermore, bioinformatics analysis and luciferase reporter assay identified that CD276 was the direct functional target of miR-187 in CRC. Genetic silencing of CD276 recapitulated similar phenotype as observed in over-expression of miR-187, and restoration of CD276 completely rescued the inhibitory effect of miR-187 in CRC cells. Taken together, our study implied the essential roles of miR-187 in suppressing CRC progression, and a novel link between miR-187 and CD276 in CRC.
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Antígenos B7/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , MicroRNAs/genética , Animais , Apoptose/fisiologia , Antígenos B7/metabolismo , Estudos de Casos e Controles , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Regulação para Baixo , Técnicas de Silenciamento de Genes , Terapia Genética , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/administração & dosagem , MicroRNAs/metabolismo , Invasividade Neoplásica , Prognóstico , Distribuição Aleatória , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Rab3D belongs to Rab protein family. Previous reports showed that the expression of Rab3D was dysregulated in various types of cancer. Rab3D belongsRab3D belongs. However, little is known about the role of Rab3D in carcinogenesis and progression of colorectal cancer (CRC). Here, we first evaluated the expression of Rab3D in 32 fresh CRC and matched normal tissues and found Rab3D was dramatically increased in CRC tissues compared to normal tissues (p<0.001). Furthermore, immunochemistry was used to investigate Rab3D expression in 300CRC tissue specimens. The expression of Rab3D significantly positively correlated with the tumor size (p=0.041), CEA level (p=0.007), tumor classification (p=0.030), lymphatic metastasis (p<0.001), distant metastasis (p=0.013) and clinical stage (p=0.003). We also demonstrated that overall survival is poor in CRC patients with high expression of Rab3D (p<0.001). Finally, we showed that Rab3D activated Akt/GSK3ß/Snail pathway and induced EMT process in colorectal cancer cells. In conclusion, this study establishes increased Rab3D expression is associated with invasiveness of CRC cells, and Rab3D expression status may serve as a reliable prognostic biomarker in CRC patients.
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Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas rab3 de Ligação ao GTP/genética , Proteínas rab3 de Ligação ao GTP/metabolismo , Idoso , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/metabolismo , Regulação para CimaRESUMO
Reprogrammed metabolism is a hallmark of cancer cells. Regulator of G-protein signaling 6 (RGS6), which is frequently down-regulated in multiple human malignancies, has been demonstrated to play a critical function in energy metabolism, cell apoptosis and tumorigenesis. However, limited knowledge is known about the expression pattern and prognostic value of RGS6 in colorectal cancer (CRC). In this study, we first observed that RGS6 mRNA and protein is commonly downregulated in 32 paired CRC tissues compared with their normal counterparts. Furthermore, by a large scale of immunohistochemical analysis in a tissue microarray containing 310 cases of CRC specimens, we demonstrated that the protein expression of RGS6 expression is downregulated in 40.97% (127/310) samples and detected that decreasing RGS6 expression is closely correlated with enhanced tumor size, CEA level, T classification, TNM stage, and easier lymphatic and distant metastasis. Meanwhile, Kaplan-Meier survival analysis showed that CRC patients with a lower RGS6 expression have a poorer clinical outcome than those with a higher RGS6 expression. Multivariate Cox regression analysis revealed that RGS6, lymphatic metastasis and distant metastasis are the independent prognostic factors for overall survival rate of CRC patients. Taken together, our studies reveal the prognostic value of RGS6 in CRC and support that RGS6 may act as a molecular target for CRC treatment.
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Neoplasias Colorretais/patologia , Regulação para Baixo , Proteínas RGS/genética , Idoso , Neoplasias Colorretais/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
ATPase family AAA domain-containing 2 (ATAD2) has been identified as a critical modulator involved in cell proliferation and invasion. The purpose of this study was to explore the expression of ATAD2 in CRC tissues as well as its relationship with degree of malignancy. Data containing three independent investigations from Oncomine database demonstrated that ATAD2 is overexpressed in CRC compared with normal tissue, and similar result was also found in 32 pairs of CRC tissues by qPCR. The protein expression of ATAD2 was examined in six CRC cell lines and 300 CRC specimens. The results showed that high expression of ATAD2 was significantly correlated with tumor size (P < 0.001), serum CEA (P = 0.012), lymph node metastasis (P = 0.018), liver metastasis (P = 0.025), and clinical stage (P = 0.004). Kaplan-Meier method suggested that higher ATAD2 protein expression significantly associated with the overall survival (OS) of CRC patients (P < 0.001) and was an independent predictor of poor OS. Functional studies showed that suppression of ATAD2 expression with siRNA could significantly inhibit the growth in SW480 and HCT116 cells. These results indicated that ATAD2 could serve as a prognostic marker and a therapeutic target for CRC.
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Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a cyclin-dependent kinase-interacting protein, which is essential for cell cycle regulation. Elevated expression of CKS2 has been demonstrated in multiple types of human malignancies. However, the clinical significance, oncogenic functions and related mechanisms of CKS2 in colorectal cancer (CRC) remain largely unexplored. In this study, data from Oncomine database revealed that CKS2 is significantly up-regulated in CRC tissues compared with their normal counterparts. Immunohistochemical analysis of a CRC tissue microarray demonstrated that elevated CKS2 expression is closely associated with enhanced TNM stage, larger tumor size and a poor prognosis in patients with CRC. Multivariate Cox regression analysis revealed that CKS2 and TNM stage are two independent prognostic factors for CRC. Suppression of CKS2 expression resulted in decreased cell viability, increased cell apoptosis, cell cycle arrest and reduced expression of cyclins in Caco-2 and SW620 cells. Furthermore, gain and loss of function studies demonstrated that CKS2 promotes cell invasion in CRC cells through regulating claudin1. Taken together, our study reveal that CKS2 is promising prognostic indicator and contributes to tumor progression in CRC, and support that CKS2-related signaling may represent a novel target for CRC therapy.
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Epithelial cell transforming sequence 2 (ECT2) is a well-studied guanine nucleotide exchange factor for the Rho family GTPase, which has been demonstrated as an oncogene in many types of human cancers. However, little is known about the prognostic value of ECT2 in colorectal cancer (CRC). In current study, we investigated the expression pattern and underlying clinical significance of ECT2 in CRC. ECT2 expression was detected in 345 CRC specimens by immunohistochemistry, and its correlation with clinicopathologic parameters and prognosis of CRC patients were analyzed. Data from Oncomine database and real-time PCR demonstrated that ECT2 expression was elevated in CRC compared with normal tissues. Among the clinical parameters analyzed, high expression level of ECT2 significantly associated with tumor size (P=0.020), serum CEA levels (P = 0.000) and TNM stage (P=0.027). Kaplan-Meier survival analysis showed that patients with high ECT2 expression had a remarkably shorter overall survival. Cox regression analysis revealed that ECT2 expression level was a significant and independent prognostic factor for overall survival rate of CRC patients. These data suggested that ECT2 is an unfavorable biomarker of prognosis in CRC and that ECT2 may be a potential therapeutic candidate for CRC treatment.
Assuntos
Biomarcadores Tumorais/biossíntese , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Idoso , Neoplasias Colorretais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas/genética , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVE: To determine whether lysosome-associated protein transmembrane-4 beta (LAPTM4B) over-expression is associated with the proliferation and invasion in colorectal cancer (CRC). METHODS: Thirty pairs of CRC tissues, containing carcinoma and adjacent tissues, were used for the examination of LAPTM4B mRNA expression by real-time quantitative PCR (qPCR) assays. Then immunohistochemistry was performed to examine LAPTM4B protein expression in 6 pairs of CRC tissues. Over-expression LAPTM4B and low-expression LAPTM4B cell models were constructed with HCT116 CRC cell lines. CCK8 assay was used to detect the proliferation and Transwell assay was used to detect the invasion of the model cells. RESULTS: qPCR and immunohistochemistry results showed that LAPTM4B expression levels in CRC were higher compared to adjacent tissues (all P<0.01). CCK8 and Transwell assays results showed that LAPTM4B promoted proliferation and invasion of HCT116 cell lines model cells (all P<0.01). CONCLUSION: LAPTM4B promotes the proliferation and invasion in CRC patients, and may be used as an important potential marker.