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BACKGROUND: Protective loop ileostomy is commonly performed in laparoscopic low anterior rectal resection to prevent the serious complications of anastomotic fistula. It is usually created at the right lower quadrant of the abdomen and another wound is required for stoma. The study aimed to evaluate the outcomes of ileostomy at the specimen extraction site (SES) and another site (AS) beside the auxiliary incision. METHODS: A retrospective analysis was conducted on 101 eligible patients with pathologically diagnosed adenocarcinoma of the rectum from January 2020 to December 2021 in the study center. According to whether the ileostomy was at the specimen extraction site, patients were divided into SES group (40 patients) and AS group (61 patients). Clinicopathological characteristics, the intraoperative details, and postoperative outcomes of the two groups were measured. RESULTS: Univariate analysis showed that the operative time was significantly shorter and the blood loss was significantly less in the SES group than in the AS group during laparoscopic low anterior rectal resection, the time to first flatus was significantly shorter, and the pain was significantly less in the SES group than in the AS group during ileostomy closure. The postoperative complications were similar in both groups. Multivariable analysis showed that ileostomy at the specimen extraction site was a significant factor influencing the operative time and blood loss of rectal resection, and influencing the pain and the time to first flatus during ileostomy closure. CONCLUSION: Compared to ileostomy at AS, protective loop ileostomy at SES was time-saving and less bleeding during laparoscopic low anterior rectal resection, and more quick to first flatus and less pain during stoma closure, and did not lead to more postoperative complications. The median incision of the lower abdomen and the left lower abdominal incision were both good sites for ileostomy.
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Laparoscopía , Neoplasias del Recto , Humanos , Ileostomía/efectos adversos , Estudios Retrospectivos , Flatulencia/complicaciones , Flatulencia/cirugía , Neoplasias del Recto/cirugía , Complicaciones Posoperatorias/etiología , Laparoscopía/efectos adversos , Anastomosis Quirúrgica/efectos adversos , DolorRESUMEN
The treatment of gastric cancer (GC) is extremely challenging; however, the specific pathogenesis of GC remains unclear. Circular RNAs (CircRNAs) are non-coding RNAs that can regulate gene expression both transcriptionally and post-transcriptionally. However, little is known about the circRNAs that are important in the progression of GC. This study identified significantly dysregulated circRNAs by analyzing gastric cancer patients and normal control tissues. The target gene was predicted using online bioinformatics tools and verified using RNA pull-down and luciferase reporter assays. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to evaluate gene and protein expression. The malignant behavior of GC cells was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, wound healing assay, Transwell invasion assay, and flow cytometry. CircPFKP is downregulated in GC tissues, and overexpression of circPFKP inhibits malignant behavior in GC cells. Bioinformatics predicted that circPFKP could bind to miR-644, and miR-644 could target disintegrin-like and metalloprotease domain-containing thrombospondin type 1 motif-like 5 (ADAMTSL5). Overexpression of circPFKP enhances the expression of ADAMTSL5 by decreasing the expression of miR-644 to suppress the growth of xenograft GC tumors in vivo and in vitro. In conclusion, the circPFKP/miR-644/ADAMTSL5 regulatory pathway inhibited the malignant progression of GC. These findings may extend our understanding of the effects of circRNAs on cancer development and provide novel targets for the diagnosis of GC.
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Proteínas ADAMTS , MicroARNs , ARN Circular , Neoplasias Gástricas , Proteínas ADAMTS/genética , Proteínas ADAMTS/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Metástasis de la Neoplasia , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
Integrative expression Quantitative Trait Loci (eQTL) analysis found that rs8180040 was significantly associated with Coiled-coil domain containing 12 (CCDC12) in colon adenocarcinoma (COAD) patients. Immunohistochemical staining and western blotting confirmed CCDC12 was highly expressed in COAD tissues, which was consistent with RNA-Seq data from the TCGA database. Knockdown of CCDC12 could significantly reduce proliferation, migration, invasion, and tumorigenicity of colon cancer cells, while exogenous overexpression of CCDC12 had the opposite effect. Four plex Isobaric Tags for Relative and Absolute Quantitation assays were performed to determine its function and potential regulatory mechanism and demonstrated that overexpression of CCDC12 would change proteins on the adherens junction pathway. Overexpressed Snail and knocked down CCDC12 subsequently in SW480 cells, and we found that overexpression of Snail did not significantly change CCDC12 levels in SW480 cells, while knockdown of CCDC12 reduced that of Snail. CCDC12 plays a significant role in tumorigenesis, development, and invasion of COAD and may affect the epithelial to mesenchymal transformation process of colon cancer cells by regulating the Snail pathway.
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Neoplasias del Colon , Enfermedad Pulmonar Obstructiva Crónica , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias del Colon/metabolismo , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , HumanosRESUMEN
PURPOSE: Protective loop ileostomy is an effective diversion measure often used to reduce the risk of anastomotic leakage. The purpose of the present study was to evaluate the surgical outcomes of the one-stitch method (OM) of protective loop ileostomy in laparoscopic low anterior resection for BMI obesity patients with rectal cancer compared with the traditional method (TM). METHODS: The patients diagnosed as rectal adenocarcinoma cases by preoperative pathology were included in this retrospective study. The subjects underwent protective loop ileostomy in laparoscopic low anterior resection from January 2016 to June 2019 in the Shandong Provincial Hospital affiliated to Shandong University. The data of loop ileostomy and stoma closure operation were retrieved from the medical cases system of the hospital. RESULTS: 242 patients were included in the present study. In the BMI obese cohort, the OM group showed a shorter operative time both in the loop ileostomy (232.5 vs. 250.0 min, p = 0.04) and stoma closure operation (102.5 vs. 115.0 min, p = 0.001) and a lower peristomal adhesion extent (p = 0.02) and a shorter median postoperative stay (6 vs. 7 days, p = 0.03) during stoma closure operation than that of the TM group. In the TM group, obese cases showed a higher operative time of stoma closure operation (115.0 vs. 95.0, p < 0.001), a higher parastomal hernia rate (p = 0.04), a higher peristomal adhesion extent (p = 0.005) and a longer postoperative stay of stoma closure operation (p = 0.02) compared with the non-obese cases, while in the OM group, no significant differences were observed between the obese and non-obese cases in terms of the above-mentioned factors. CONCLUSIONS: The OM exhibited more advantages than TM, notably in BMI obesity patients.
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Adenocarcinoma/cirugía , Índice de Masa Corporal , Ileostomía/métodos , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Obesidad/fisiopatología , Neoplasias del Recto/cirugía , Adenocarcinoma/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias del Recto/patología , Estudios RetrospectivosRESUMEN
Insulin resistance (IR) is the most common pathophysiological change in patients with type 2 diabetes mellitus (T2DM). Several recent studies have suggested that the gut microbiome and microbial metabolites are involved in the pathogenesis of IR. Bariatric surgery, as an effective treatment for T2DM, can markedly alleviate IR through mechanisms that have not been elucidated. In this review, we summarize the current evidence on the changes in the gut microbiome and microbial metabolites (including lipopolysaccharide, short-chain fatty acids, branched-chain amino acids, aromatic amino acids, bile acids, methylamines, and indole derivatives) after bariatric surgery. Additionally, we discuss the mechanisms that correlate the changes in microbial metabolites with the postoperative alleviation of IR. Furthermore, we discuss the prospect of bariatric surgery as a treatment for T2DM.
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Cirugía Bariátrica , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistencia a la Insulina , Obesidad Mórbida , Diabetes Mellitus Tipo 2/cirugía , Humanos , Obesidad Mórbida/cirugíaRESUMEN
Genome-wide association studies of colorectal cancer (CRC) have identified two risk SNPs. The characterization of these risk regions in diverse racial groups with different linkage disequilibrium structure would aid in localizing the causal variants. Herein, fine mapping of the established CRC loci was carried out in 1,508 cases and 1,482 controls obtained from the Han Chinese population. One distinct association signal was identified at these loci, where fine mapping implicated rs1010208 as a functional locus. Next, the candidate target genes of functional SNP rs1010208 were analyzed using data from TCGA databases by expression quantitative trait loci analysis method; the data from Peking University People's Hospital were utilized for verification. The dual-luciferase reporter system analysis confirmed that rs1010208 is a regulatory region that can be mutated to decrease the expression of HINT1, resulting in proliferation and invasiveness of CRC.
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BACKGROUND: Protective loop ileostomy is widely performed during rectal resection surgery. The study aimed to introduce the one-stitch method (OM) of protective loop ileostomy in laparoscopic low anterior resection and compare this new method with the traditional method (TM). MATERIALS AND METHODS: A retrospective analysis was conducted on 109 patients with pathologically diagnosed adenocarcinoma of the rectum from January 2017 to December 2018 in the study centre, and the intraoperative details and postoperative outcomes of the two groups were measured. RESULTS: A total of 95 patients were included: 54 underwent protective loop ileostomy with the TM, while 41 underwent surgery utilizing the OM. Univariate analysis demonstrated that the operative times of resection and closure were significantly shorter (resection, 200.0 vs. 227.5 min, P = 0.028; closure, 70.0 vs. 92.5 min, P = 0.018) and the peristomal adhesions during closure were milder (P = 0.007) in the OM group than in the TM group. The postoperative complications were similar in both groups. In multivariate analysis, the OM (OR 0.352, 95% CI = 0.155-0.799, P = 0.013) was a significant factor influencing the operative time of resection. The peristomal adhesion extent was the only independent risk factor for the stoma closure time (mild, OR 0.036, 95% CI = 0.010-0.129, P < 0.001; moderate, OR 0.128, 95% CI = 0.033-0.494, P = 0.003). No significant predictive factor of peristomal adhesion extent was identified in multivariable analysis. CONCLUSION: The OM of protective loop ileostomy in laparoscopic low anterior resection was time-saving, simple and easy to popularize and did not lead to more postoperative complications than the TM.
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Adenocarcinoma/cirugía , Ileostomía/métodos , Laparoscopía/métodos , Proctectomía/métodos , Neoplasias del Recto/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/etiología , Recto/patología , Recto/cirugía , Estudios Retrospectivos , Factores de Riesgo , Adherencias Tisulares/etiología , Resultado del TratamientoRESUMEN
Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma via activating the MAPK signaling pathway.
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Adenocarcinoma/tratamiento farmacológico , Terapia Molecular Dirigida , Receptor Tipo 5 de Factor de Crecimiento de Fibroblastos/metabolismo , Neoplasias del Recto/tratamiento farmacológico , Adenocarcinoma/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Receptor Tipo 5 de Factor de Crecimiento de Fibroblastos/genética , Neoplasias del Recto/patología , Ensayo de Tumor de Célula MadreRESUMEN
Colorectal cancer (CRC) is the third most common cancer worldwide and its treatment remains a challenge. Effective control of cell survival and proliferation is critical in the prevention of oncogenesis and successful treatment of cancer. Long non-coding RNAs (lncRNAs) have emerged as primary regulators of carcinogenesis. Growth arrest specific 5 (GAS5), a lncRNA, is known to be aberrantly expressed in several types of cancer, however, the role of GAS5 in CRC remains unclear. In the present study, GAS5 mRNA expression was measured in CRC and adjacent normal mucosa tissue samples from 53 patients using reverse transcription-quantitative polymerase chain reaction analysis, in addition to seven CRC cell lines. GAS5 mRNA expression was observed to be markedly downregulated in human CRC tissues and cell lines. Decreased GAS5 expression was associated with an increase in tumor diameter [odds ratio (OR), 0.176 (95% CI, 0.053-0.586); P=0.003] and later tumor-node-metastasis stage [OR, 0.261 (95% CI, 0.083-0.819); P=0.019]. Patients with decreased GAS5 expression exhibited decreased overall survival rates compared with patients with increased GAS5 expression (P=0.015). The Cox proportional hazards model demonstrated that downregulated GAS5 expression was an independent prognostic factor for CRC (hazard ratio, 0.236; 95% confidence interval, 0.067-0.827; P=0.024). Functional assays demonstrated that overexpression of GAS5 inhibited cell proliferation and survival, and induced G0/G1 cell cycle arrest and apoptosis; however, knockdown of GAS5 expression enhanced cell proliferation, and reduced G0/G1 arrest and apoptosis. In conclusion, the results of the present study suggest that GAS5 is essential in the control of apoptosis and cell growth in CRC. Therefore, GAS5 may represent a novel prognostic and diagnostic marker of CRC, in addition to being a potential therapeutic target.
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The progression of distant metastasis cascade is a multistep and complicated process, frequently leading to a poor prognosis in cancer patients. Recently, growing evidence has indicated that deregulation of microRNAs (miRNAs) contributes to tumorigenesis and tumor progression in colorectal cancer (CRC). In the present study, by comparing the miRNA expression profiles of CRC tissues and corresponding hepatic metastasis tissues, we established the downregulation of miR-199b in CRC metastasis tissues. The decrease in miR-199b expression was significantly correlated to late TNM stage and distant metastasis. Moreover, Kaplan-Meier curves showed that CRC patients with high expression level of miR-199b had a longer median survival. Functional assays results indicated that the restoration of miR-199b considerably reduced cell invasion and migration in vitro and in vivo, and increased the sensitivity to 5-FU and oxaliplatin. Further dual-luciferase reporter gene assays revealed that SIRT1 was the direct target of miR-199b in CRC. The expression of miR-199b was inversely correlated with SIRT1 in CRC specimens. SIRT1 knockdown produced effects on biological behavior that were similar to those of miR-199b overexpression. Furthermore, through Human Tumor Metastasis PCR Array we discovered KISS1 was one of the downstream targets of SIRT1. Silencing of SIRT1 upregulated KISS1 expression by enhancing the acetylation of the transcription factor CREB. The latter was further activated via binding to the promoter of KISS1 to induce transcription. Thus, we concluded that miR-199b regulates SIRT1/CREB/KISS1 signaling pathway and might serve as a prognosis marker or a novel therapeutic target for patients with CRC.
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Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , Invasividad Neoplásica/genética , Sirtuina 1/metabolismo , Adulto , Anciano , Animales , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Regulación hacia Abajo , Femenino , Xenoinjertos , Humanos , Estimación de Kaplan-Meier , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/patología , Pronóstico , Sirtuina 1/genéticaRESUMEN
BACKGROUND: Recent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown. METHODS: We examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1. RESULTS: Our data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3'-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth. CONCLUSIONS: Our findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.
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Biomarcadores de Tumor/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Neoplasias Colorrectales/genética , MicroARNs/biosíntesis , Anciano , Animales , Apoptosis/genética , Biomarcadores de Tumor/genética , Moléculas de Adhesión Celular/genética , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Proteínas de la Membrana , Ratones , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica/genética , Pronóstico , Proteínas de Unión al ARN , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Although genome-wide association studies have identified many risk loci associated with colorectal cancer, the molecular basis of these associations are still unclear. We aimed to infer biological insights and highlight candidate genes of interest within GWAS risk loci. We used an in silico pipeline based on functional annotation, quantitative trait loci mapping of cis-acting gene, PubMed text-mining, protein-protein interaction studies, genetic overlaps with cancer somatic mutations and knockout mouse phenotypes, and functional enrichment analysis to prioritize the candidate genes at the colorectal cancer risk loci. Based on these analyses, we observed that these genes were the targets of approved therapies for colorectal cancer, and suggested that drugs approved for other indications may be repurposed for the treatment of colorectal cancer. This study highlights the use of publicly available data as a cost effective solution to derive biological insights, and provides an empirical evidence that the molecular basis of colorectal cancer can provide important leads for the discovery of new drugs.
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Reposicionamiento de Medicamentos , Estudio de Asociación del Genoma Completo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Farmacogenética , Alelos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Biología Computacional/métodos , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Genómica/métodos , Humanos , Anotación de Secuencia Molecular , Mutación , Neoplasias/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple , Mapeo de Interacción de Proteínas/métodos , Mapas de Interacción de Proteínas , Sitios de Carácter CuantitativoRESUMEN
Tumor growth cascade is a complicated and multistep process with numerous obstacles. Until recently, evidences have shown the involvement of microRNAs (miRNAs) in tumorigenesis and tumor progression of various cancers, including colorectal cancer (CRC). In this study, we explored the role of miR-194 and its downstream pathway in CRC. We acquired data through miRNA microarray profiles, showing that the expression of miR-194 was significantly suppressed in CRC tissues compared with corresponding noncancerous tissues. Decreased miR-194 expression was obviously associated with tumor size and tumor differentiation, as well as TNM stage. Both Kaplan-Meier and multivariate survival analysis showed that downregulated miR-194 was associated with overall survival. Moreover, functional assays indicated that overexpression of miR-194 in CRC cell lines inhibited cell proliferation both in vitro and in vivo. In addition, using dual-luciferase reporter gene assay, we found MAP4K4 was the direct target of miR-194. Silencing of MAP4K4 resulted in similar biological behavior changes to that of overexpression of miR-194. We also observed through Human Gene Expression Array that MDM2 was one of the downstream targets of MAP4K4. Knockdown of MAP4K4 downregulated MDM2 expression through transcription factor c-Jun binding to the -1063 to -1057 bp of the promoter. These results suggest that miR-194, regulating the MAP4K4/c-Jun/MDM2 signaling pathway, might act as a tumor suppressor and serve as a novel target for CRC prevention and therapy.
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Neoplasias Colorrectales/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , MicroARNs/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Regiones no Traducidas 3' , Animales , Apoptosis , Secuencia de Bases , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Estimación de Kaplan-Meier , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Análisis Multivariante , Trasplante de Neoplasias , Pronóstico , Regiones Promotoras Genéticas , Modelos de Riesgos Proporcionales , Unión Proteica , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-jun/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Interferencia de ARN , Transducción de SeñalRESUMEN
It is not known whether low-dose radioiodine is as effective as high-dose radioiodine for treating patients with differentiated thyroid cancer after surgery. This study compared ablation success rates of different doses of radioiodine in patients with differentiated thyroid cancer after thyroidectomy. Fifteen randomized controlled trials were obtained from PubMed, Embase, and Cochrane Library (1966 to February 2013). Stata version 12.0 was used to pool the outcomes. Mantel-Haenszel (MH) and inverse variance (IV) methods were used in a fixed-effects and random-effects model, respectively. The relative risk (RR) with 95% confidence interval (CI) was used to compare the success rates of different doses of radioiodine. There were a total of 3,046 patients. The pooled RR for comparing ablation success with low- and high-dose radioiodine was 0.90 (95% CI 0.83-0.98, IV). Excluding a study with a distinctive outcome, sensitivity analysis showed that the pooled RR was 0.95 (95% CI 0.92-0.99, MH). In subgroup analysis, the pooled RR of three studies that only administrated radioiodine to patients with pT2-4 cancer was 0.93 (95% CI 0.83-1.04, MH); the pooled RR of five studies with total thyroidectomy for all patients was 0.96 (95% CI 0.92-1.00, MH); and the pooled RR of four studies that used thyrotropin α to stimulate serum thyrotropin was 0.96 (95% CI 0.90-1.02, MH). The pooled RRs for comparing ablation success for moderate-dose versus high-dose and low-dose radioiodine were 0.94 (95% CI 0.85-1.04, IV) and 0.87 (95% CI 0.73-1.04, IV), respectively. Low-dose radioiodine can be used in patients undergoing total thyroidectomy. For those who receive insufficient surgical treatment, high-dose radioiodine is more appropriate.
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Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Adulto , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , TiroidectomíaRESUMEN
The aim of this study was to identify the best cutoff points for lymph node classification to improve the prognostic prediction of gastric cancer in China. Patients who had undergone surgery for gastric cancer were retrospectively evaluated in two high-volume institutions from Peking University People's Hospital (PKUPH, N=503) and Affiliated Hospital of Qingdao University (AHQU, N=1,003). The prognosis of these patients was assessed according to the number of metastatic lymph nodes with an increment of one node at one time. A new lymph node classification was proposed based on the relation between prognosis and the number of metastatic lymph nodes. According to the prognostic value, the proposed node (N) stage was categorized as N0 (no regional LNs metastasis), N1 (1-3 involved regional LNs), N2 (4-6 involved regional LNs), and N3 (≥7 involved regional LNs). The hazard ratio for the proposed N classification increased steadily and reasonably compared with the 7th edition. Moreover, the Cox regression multivariate analysis showed that the proposed N classification was superior to the 7th N classification as an independent prognostic factor. The proposed N category was superior to 7th edition N category of the American Joint Committee on Cancer (AJCC) for assessing the prognosis for gastric cancer patients in China.
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Adenocarcinoma/clasificación , Adenocarcinoma/secundario , Ganglios Linfáticos/patología , Neoplasias Gástricas/clasificación , Neoplasias Gástricas/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Anciano , China , Femenino , Gastrectomía , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Tasa de SupervivenciaRESUMEN
Genome-wide association studies have identified many risk loci associated with colorectal cancer. Strategies integrating biological data sets with GWAS results will provide insights into the roles of risk single-nucleotide polymorphisms. We performed expression quantitative trait locus-based analyses using the information provided in The Cancer Genome Atlas. Analysis of the cis-expression quantitative trait loci (eQTLs) of 18 previously reported colorectal cancer risk loci resulted in the discovery of five variants that were significantly associated with gene expressions. Analysis of the trans-eQTLs identified three risk loci that affect the expression levels of a neighboring transcription factor, MYC. These findings provide a more comprehensive picture of gene expression determinants in colorectal cancer and insights into the underlying biology of risk loci.
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Neoplasias Colorrectales/genética , Expresión Génica , Predisposición Genética a la Enfermedad , Sitios de Carácter Cuantitativo , Biología Computacional/métodos , Bases de Datos de Ácidos Nucleicos , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Transcripción GenéticaRESUMEN
BACKGROUND: Sirtuin 1 (SIRT1) has been reported to have diverse roles in various biological processes through deacetylation of histone and nonhistone proteins. However, the correlations among SIRT1 protein expression, clinicopathological parameters, and survival of colorectal cancer patients remain unclear. METHODS: SIRT1 protein expression was measured by immunohistochemistry in a paraffin-embedded tissue microarray, including 120 paired colorectal cancer and normal mucosa tissues. The correlations among SIRT1 protein expression, clinicopathological features, and prognosis were analyzed. RESULTS: All samples (100%) were positive for SIRT1, with variable staining in the cytoplasm rather than in the nucleus. There was significant difference in SIRT1 overexpression between adenocarcinomas and normal mucosal tissue (P < 0.01, χ(2) test). SIRT1 overexpression was more frequently observed in advanced-stage tumors (P = 0.046, 0.002, χ(2) test). SIRT1 overexpression was significantly correlated with poor overall survival (P = 0.013, log-rank test) and diseasefree survival (P = 0.012, log-rank test). CONCLUSIONS: SIRT1 overexpression correlated with advanced stage and poor prognosis. SIRT1 may play an important role in the progression of colorectal cancer.
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Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Sirtuina 1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Sirtuin 1 (SIRT1) has been reported to have diverse roles in various biological processes through deacetylation of histone and nonhistone proteins. However, the correlations between SIRT1 protein expression, clinicopathological parameters, and survival of colorectal cancer patients remain unclear. SIRT1 protein expression in a paraffin-embedded tissue microarray, including 13 benign adenomas, nine liver metastasis tissues, and 120 paired colorectal cancer and normal mucosa tissues, was measured by immunohistochemistry. SIRT1 mRNA and protein expression in colon cancer cell lines with different metastatic potential and normal colon cells were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The correlations between SIRT1 protein expression, clinicopathological features, and prognosis were analyzed. All samples (100 %) were positive for SIRT1, with variable staining in the cytoplasm rather than the nucleus. There was significant difference in SIRT1 overexpression between adenocarcinomas and normal mucosal tissues (P < 0.01, χ(2) test). SIRT1 overexpression was more frequently observed in advanced-stage tumors and lymph node or liver metastases (P = 0.046, 0.002, and 0.004, respectively, χ(2) test). SIRT1 expression was also significantly elevated in the more aggressive colon cancer cell line SW620. SIRT1 overexpression was significantly correlated with poor overall survival (P = 0.013, log-rank test) and disease-free survival (P = 0.012, log-rank test). SIRT1 overexpression was correlated with advanced-stage and poor prognosis. SIRT1 may play an important role in the progression of colorectal cancer.