AIM:To investigate the targeted inhibition of proliferation and migration of SW620 human colon cancer cells by upregulating miRNA-145 (miR-145). METHODS:Forty-five samples of colon cancer tissues and 45 normal control samples were obtained from the biological database of the First Affiliated Hospital of Liaoning Medical University.We performed quantitative analysis of miR-145 and N-ras expression in tissues; reverse transcriptase polymerase chain reaction analysis of miR-145 expression in SW620 colon cancer cells and normal colonic epithelial cells; construction of miR-145 lentiviral vector and determination of miR-145 expression in SW620 cells transduced with miR-145 vector; analysis of the effect of miR-145 overexpression on SW620 cell proliferation; analysis of the effect of miR-145 overexpression on SW620 cell migration using a wound healing assay; and analysis of the effect of
There is no conclusion about the most important contributor to the upswing of locally advanced colorectal cancer (LACRC) survival.Data from the Surveillance, Epidemiology, and End Results (SEER) database was extracted to identify colorectal adenocarcinoma cancer patients at stage II and III diagnosed in the two periods 1989-1990 and 2009-2010. The statistical methods included Pearson's chi-squared test, log-rank test, Cox regression model and propensity score matching.The Cox regression model showed that hazard ratio (HR) of non-surgery dropped from 11.529 to 3.469 in right colon cancer (RCC), 5.214 to 2.652 in left colon cancer (LCC) and 3.275 to 3.269 in rectal cancer (RC) from 1989-1990 to 2009-2010. The 95% confidence intervals (CIs) for surgical resection in 2009-2010 were narrower than those in 1989-1990. HR became greater in LACRC without chemotherapy (from 1.337 to 1.779 in RCC, 1.269 to 2.017 in LCC, 1.317 to 1.811 in RC). There was no overlapping about the 95% CI of chemotherapy between the two groups. The progress of surgery was not linked to the improvement of overall survival (OS) of RCC (p = 0.303) and RC (p = 0.660). Chemotherapy had a significant association with OS of all colorectal cancer (CRC) patients (p = 0.017 in RCC; p = 0.006 in LCC; p = 0.001 in RC).Advancements in chemotherapy regimen were the main contributor to the upswing of CRC survival. The improvements in surgery had a limited effect on improvements in CRC survival.
The aim of this study was to analyse the landscape of publications on rectal cancer (RC) over the past 25 years by machine learning and semantic analysis.Publications indexed in PubMed under the Medical Subject Headings (MeSH) term 'Rectal Neoplasms' from 1994 to 2018 were downloaded in September 2019. R and Python were used to extract publication date, MeSH terms and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet allocation was applied to analyse the text from the articles' abstracts to identify more specific research topics. Louvain algorithm was used to establish a topic network resulting in identifying the relationship between the topics.A total of 23,492 papers published were identified and analysed in this study. The changes of research focus were analysed by the changing of MeSH terms. Studied contents extracted from the publications were divided into five areas, including surgical intervention, radiotherapy and chemotherapy intervention, clinical case management, epidemiology and cancer risk as well as prognosis studies.The number of publications indexed on RC has expanded rapidly over the past 25 years. Studies on RC have mainly focused on five areas. However, studies on basic research, postoperative quality of life and cost-effective research were relatively lacking. It is predicted that basic research, inflammation and some other research fields might become the potential hotspots in the future.
A growing body of evidence suggests that the histone demethylase-lysine demethylase 5 (KDM5) family is associated with drug resistance in cancer cells. However, it is still not clear whether KDM5 family members promote chemotherapy resistance in pancreatic ductal adenocarcinomas (PDAC). Comprehensive bioinformatics analysis was performed to investigate the prognostic value, and functional mechanisms of KDM5 family members in PDAC. The effects of KDM5 family members on drug resistance in PDAC cells and the relationship with CD44, as a stem cell marker, were explored by gene knockout and overexpression strategies. Finally, our findings were validated by functional experiments such as cell viability, colony formation and invasion assays. We found that the expression of KDM5A/C was significantly higher in gemcitabine-resistant cells than in sensitive cells, consistent with the analysis of the GSCALite database. The knockdown of KDM5A/C in PDAC cells resulted in diminished drug resistance, less cell colonies and reduced invasiveness, while KDM5A/C overexpression showed the opposite effect. Of note, the expression of KDM5A/C changed accordingly with the knockdown of CD44. In addition, members of the KDM5 family function in a variety of oncogenic pathways, including PI3K/AKT and Epithelial-Mesenchymal Transition. In conclusion, KDM5 family members play an important role in drug resistance and may serve as new biomarkers or potential therapeutic targets in PDAC patients.
This study is aimed at investigating predictive and prognostic factors of synchronous colorectal lung-limited metastasis (SCLLM) based on The Surveillance, Epidemiology, and End Results (SEER) database.A multivariate logistic regression model was constructed to identify independent predictors of SCLLM. A multivariate Cox proportional hazards regression model was used to distinguish independent prognostic factors.This study enrolled 168,007 colorectal cancer (CRC) patients without metastatic diseases and 1,298 cases with SCLLM. Eight features, involving race, tumor location, pathological grade, histological type, T stage, N stage, and tumor size as well as CEA, could be used as the independent predictors. As the nomogram shown, the T4 stage contributed the most to SCLLM, followed by the N2 stage, elevated CEA, and rectal cancer. A multivariate regression analysis discriminated 9 independent prognostic factors, including age, race, marital status, pathological grade, T stage, colectomy/proctectomy, chemotherapy, CEA, and TD. The prognostic nomogram illustrated that nonresection/NOS played as the poorest prognostic factor, followed by nonchemotherapy, ≥75-year old and T4 stage. The cumulative survival curves revealed the influence of each prognostic factor on survival after controlling the other variables.This study identified independent predictors and prognostic factors for SCLLM based on a large database of the United States. The predictors and prognostic factors can provide supporting evidence for the prevention and treatment of SCLLM.
Assess the risk of synchronous metastasis and establish a nomogram in patients with GISTs.Surveillance, Epidemiology and End Results database (2004-2014) was accessed. With the logistic regression model as the basis, a nomogram was constructed.7,256 target patients were contained in our study. The nomogram discrimination for mGIST prediction revealed that tumor size contributed most to synchronous metastasis, followed by lymph nodes, extension, pathologic grade, tumor location, and mitotic count. C-index values of predictions were 0.821 (95% CI, 0.805-0.836) and 0.815 (95% CI, 0.800-0.831), and Brier score were 0.109 and 0.112 in training and validation group, respectively. The value of area under the ROCs were 0.813 (p < 0.001) in the primary cohort and 0.819 (p < 0.001) in the validation cohort. Through the calibration curves (as seen in the figures), nomogram prediction proved to have excellent agreement with actual metastatic diseases.A new nomogram was created that can evaluate synchronous metastatic diseases in patients with GISTs.
Slingshot 1 protein (SSH1) plays a critical role in cytoskeleton dynamic regulation. Increasing evidence suggest that SSH1 expression is upregulated in several cancers and relates to tumor progression and drug resistance. Here, we evaluated the role of SSH1 in colorectal cancer (CRC) development and its prognostic value in patients with CRC.SSH1 expression was examined by quantitative real-time polymerase chain reaction, western blot analysis, or immunohistochemistry. The association between SSH1 expression and clinical characteristics and prognosis was evaluated. Stable SSH1 knockdown cells were used for in vitro assays and xenograft models. Correlation between SSH1 expression and epithelial-mesenchymal transition (EMT) was analyzed by western blot and online data analysis.SSH1 expression was upregulated in cancer tissue compared with paired non-cancerous tissue in patients with CRC. SSH1 expression level in CRC tissue was associated with tumor stage, lymph node metastasis, and correlated with poor prognosis as indicated by univariate and multivariate analyses. In vitro, loss of SSH1 impaired colony formation, migration, and invasion of CRC cells. In vivo data suggest that SSH1 could promote the progression and metastasis of CRC. Interestingly, E-cadherin, ZEB1, and Snail, which are markers of EMT, had a significant expression correlation with SSH1.SSH1 expression is associated with CRC progression and predicts poor prognosis. SSH1 may promote CRC tumor progression by regulating EMT.
To analyze the effects of primary tumor resection and metastatic lesion resection on the survival of metastatic small intestinal tumors.The research subjects were patients with metastatic small bowel tumors identified from 2004 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching and Kaplan-Meier analyses were performed to analyze the effect of surgery on the prognosis.A total of 4,034 patients from the SEER database were analyzed. Both before and after the propensity score-matching analysis, the prognosis of patients who underwent primary tumor surgery and metastatic surgery was better than that of patients who did not undergo surgery; all were patients with metastatic small bowel adenocarcinoma (mSIA) or metastatic small intestinal neuroendocrine tumors (mSI-NETs) (all p < .005). Patients with mSIA and adequate lymph node dissection had a longer prognosis than mSIA patients with inadequate lymph node dissection, but this survival benefit was not present in mSI-NET patients. It made no difference in the prognosis of mSIA and mSI-NETs whether localized surgery or intestine-ectomy was performed. Patients with mSIA who underwent primary and metastatic excision plus chemotherapy had the best overall survival and cancer-specific survival rates, whereas mSI-NET patients who underwent primary and metastatic excision had the best overall survival and cancer-specific survival rates (all p < .001).In these carefully selected patients, primary tumor resection and/or metastatic lesion resection significantly improved the survival rates for patients with mSIA and mSI-NETs. The mSIA patients with resectable primary tumors seemed to require a sufficient number of lymph node dissections more than the patients with well-differentiated mSI-NETs.
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