Abstact
Background and Aim
The gut microbiota plays a pivotal role in the intestinal diseases. Fecal microbiota transplantation (FMT) might be a rescue therapy for refractory inflammatory bowel ...disease. This study aimed to evaluate the safety, feasibility, and efficacy of FMT through mid‐gut for refractory Crohn's disease (CD).
Methods
We established standardized laboratory protocol and clinical work flow for FMT. Only refractory CD patients with Harvey–Bradshaw Index (HBI) score ≥ 7 were enrolled for this study. All included patients were treated with single FMT through mid‐gut and assessed during follow‐up.
Results
Metagenomics analysis showed a high concordance between feces sample and purified fecal microbiota from same donors. Standardized fecal microbiota preparation and clinical flow significantly simplified the practical aspects of FMT. Totally, 30 patients were qualified for the present analysis. The rate of clinical improvement and remission based on clinical activity at the first month was 86.7% (26/30) and 76.7% (23/30), respectively, which was higher than other assessment points within 15‐month follow‐up. Patients' body weight increased after FMT, and the lipid profile improved as well. FMT also showed a fast and continuous significant effect in relieving the sustaining abdominal pain associated with sustaining CD.
Conclusion
This is a pilot study with the largest sample of patients with refractory CD who underwent single FMT. The results demonstrated that FMT through mid‐gut might be a safe, feasible, and efficient rescue therapy for refractory CD.
Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could ...regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients’ clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.
Background
Submucosal tunneling endoscopic resection (STER) and endoscopic submucosal excavation (ESE) were recently introduced to cure submucosal tumors (SMTs) originating from the muscularis ...propria (MP) layer. This study aimed to compare clinical performance and safety of STER and ESE in treating esophageal SMTs originating from the MP layer.
Methods
From January 2011 to December 2017, retrospective data collection and follow-up were applied for all STER or ESE cases with esophageal SMTs originating from the MP layer in our endoscopy center, including clinical characteristics, procedure success, efficacy, and adverse events. Subgroup analysis was further done based on tumor size and origin.
Results
90 STER and 77 ESE were enrolled in this study. There were no significant difference for patient characteristics, procedure performance, and complications for ESE and STER intervention (
P
> 0.05). STER was faster than ESE (3.90 mm
2
/min vs 2.82 mm
2
/min,
P
< 0.05). For large tumors (≥ 20 mm), both techniques had the similar performance (
P
> 0.05), while STER led to the shorter hospitalization (4.0d vs 7.0d,
P
< 0.05) and lower postoperative complication (16.3% vs 45.5%,
P
< 0.05). For small tumors (< 20 mm), STER achieved faster operation (STER vs ESE, 2.57 mm
2
/min vs 1.83 mm
2
/min,
P
< 0.05). Regardless of tumor origin, there were no significant difference for both techniques, but STER resulted in short hospitalization for SMTs from the deep MP layer (STER vs ESE, 5.0d vs 7.0d,
P
< 0.05). During the follow-up, 2 residual and 4 recurrence occurred in the STER group, as well as 1 residual and 2 recurrence in the ESE group.
Conclusions
Both STER and ESE were effective for treating esophageal SMTs originating from the MP layer. STER might be better due to its faster operation, less complications, and shorter hospitalization.
Recently, long non-coding RNA (lncRNA) MIAT has been demonstrated as an oncogenic gene in several types of cancer. However, the role and mechanism of MIAT in colorectal cancer (CRC) have not been ...investigated.
Real-time PCR was used to measure MIAT expression in CRC tissues and cells. Small interfering RNA specific for MIAT (si-MIAT) was used to down-regulate MIAT expression in CRC cells. The interaction of MIAT and miR-132 was measured by RNA pull-down assay. The effect of si-MIAT on CRC cells apoptosis and metastasis were measured by flow cytometry assay, invasion and migration assay, respectively.
In present study, we found that MIAT was highly expressed in CRC tissues and cells. MIAT knockdown inhibited proliferation, migration and invasion and enhanced apoptosis of CRC cells. Further, we demonstrated that MIAT acted as a competing endogenous RNA for miR-132, antagonized its functions, and resulted in the de-repression of its target gene Derlin-1, which acted as an oncogene in promoting growth and metastasis of CRC cells. In LOVO and SW480 cells with si-MIAT, miR-132 inhibitor resulted in an increase of cell proliferation, migration and invasion and a decrease of cell apoptosis, which was partially abolished by transfection of Derlin-1 shRNA.
Our data indicated that highly expressed MIAT was an oncogenic lncRNA that promoted the growth and metastasis of CRC through miR-132/Derlin-1 axis.
Background
Benign esophageal strictures are a frequent complication after esophageal surgery or extensive endoscopic submucosal dissection. Endoscopic dilation is the preferred treatment in clinical ...practice. However, the allocation of time for each dilation is unclear. The aim of this study was to evaluate the appropriate duration of endoscopic dilation for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.
Methods
Patients with benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection between July 2010 and July 2018 were retrospectively included in this study. According to the dilation time (1, 3, 5 min), patients were divided into three groups. The clinical effects and adverse events were compared among the three groups.
Results
Altogether, 57 patients, including 21 in the 1-min group, 18 in the 3-min group and 18 in the 5-min group, were included. All patients underwent endoscopic treatment successfully. The stricture recurrence rate was 76.19% in the 1-min group, 55.56% in the 3-min group and 61.11% in the 5-min group. The median overall dysphagia-free period was 2.60 (range, 0.80–12.00) months in the 1-min group, 6.60 (range, 1.80–12.00) months in the 3-min group and 6.25 (range, 2.40–12.00) months in the 5-min group (
P
<
0.05
). For patients who developed stricture recurrence, the mean dysphagia-free periods were 2.26 ± 1.27 months, 4.00 ± 1.76 months and 4.23 ± 1.63 months, respectively (
P
<
0.05
). The dysphagia-free periods were comparable between the 3- and 5-min groups and were longer than those in the 1-min group. Muscle layer damage occurred in two patients (11.11%) in the 5-min group and in no patients in the other two groups.
Conclusion
Three minutes was considered a safe and effective dilation duration for benign esophageal strictures after esophageal surgery or endoscopic submucosal dissection.
Colorectal cancer (CRC), ranking third in cancer prevalence and second in mortality worldwide, is mainly derived from colorectal adenoma (CRA). CRA is a common benign disease in the intestine with ...rapidly increasing incidence and malignant potential. Therefore, this study aimed to recognize significant biomarkers and original pathogenesis in CRA.
Transcriptome data of GSE8671, GSE37364, and GSE15960 were downloaded from the Gene Expression Omnibus (GEO) datasets, and differentially expressed genes (DEGs) were screened. Functional pathways enrichment, protein-protein interaction (PPI) network, stem-correlation analysis, CIBERSORT, risk score and survival analyses were performed. RT-qPCR and immunohistochemical staining were applied to verify our results. RESULTS: Screening for significant DEGs in each dataset, we identified 230 robust DEGs, including 127 upregulated and 103 downregulated genes. Functional pathways enrichment showed that these DEGs were distinctly enriched in various tumor-associated pathways, such as growth factor activity, extracellular structure organization, neutrophil activation, and inflammatory response. We filtered out two hub genes via STRING and Modules analysis, including CA2 and HSD11B2. Stem-correlation analysis displayed that hub genes were negatively associated with stem-related genes (Olfm4, CD44, CCND1 and MYC). The CIBERSORT algorithm indicated that Macrophage2, activated mast cells, and Neutrophils promoted CRA progression through inflammation. Survival analysis showed that CA2 and HSD11B2 were positively associated with survival outcomes in CRC.
Our study has successfully identified the critical role of two core genes in the development and oncogenesis of CRA, which provides novel insight into the underlying pathogenesis, potential biomarkers and therapeutic targets.
Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, ...proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.
To know the effect of age on survival outcome in operated and non-operated patients with colon cancer.
From the Surveillance, Epidemiology, and End Results database, we identified 123,356 patients ...with colon cancer who were diagnosed between 1996 and 2005, grouped them as older or younger than 40 years and analyzed their 5-year cancer-specific survival (CSS) data, along with some risk factors, using Kaplan-Meier methods and multivariable Cox regression models.
The younger group had significantly higher pathological grades (P<0.001), more mucinous and signet-ring histology (P<0.001), advanced AJCC stage (P<0.001), and were more likely to undergo surgery (P<0.001). For surgically treated patients, age did not significantly affect 5-year CSS (younger: 66.7%; older: 67.3%; P = 0.86). Further analysis showed that age was an independent prognostic factor in stage I-IV disease (stage I: P = 0.001; P<0.001 for stages II-IV, in both uni- and multivariate analyses), but not for patients with unknown disease stage (P = 0.52). For non-surgically treated patients, age significantly affected 5-year CSS (younger: 16.2%; older: 12.9%; P<0.001) in univariate analysis; and was an independent prognostic factor (P<0.001) in multivariate analysis.
The CSS rate for younger CC patients was at least as high as for older patients, although they presented with higher proportions of unfavorable factors and more advanced disease.
Autophagy is an evolutionarily conserved catabolic mechanism to maintain energy homeostasis and to remove damaged cellular components, which plays an important role in the survival of various cells. ...Inhibiting autophagy is often applied as a new strategy to halt the growth of cancer cells.
The effect of FOXO1 gene on cellular function and apoptosis and its underlying mechanisms were investigated in cultured QBC939 cells by the methylthiazoletetrazolium (MTT) assay, western blot, DCFDA mitochondrial membrane potential, and ATP content measurement. FOXO1 siRNA was applied to down-regulate FOXO1 expression in QBC939 cells.
Here we reported that FOXO1, acetylation of FOXO1 (Ac-FOXO1) and the following interaction between Ac-FOXO1 and Atg7 regulated the basal and serum starvation (SS)-induced autophagy as evidenced by light chain 3 (LC3) accumulation and p62 degration. Either treatment with FOXO1 siRNA or resveratrol, a sirt1 agonist, inhibited autophagic flux, resulting in oxidative stress, mitochondrial dysfunction (MtD) and apoptosis in QBC939 cells, which were attenuated by enhancing autophagy with rapamycin. On the contrary, inhibiting autophagic flux with 3-MA worsened all these effects in QBC939 cells.
Taken together, our study for the first time identified FOXO1 as a potential therapeutic target to cure against human cholangiocarcinoma via regulation of autophagy, oxidative stress and MtD.
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