Journal of Buon最新文献

Purpose: Recent studies have manifested that bone marrow mesenchymal stem cells (BMSCs) derived exosomes affect the progression of tumors through carrying endogenous molecules. To explore the role of BMSCs-derived exosomes carrying abundant micro ribonucleic acid (miR)-126-3p in non-small-cell lung cancer (NSCLC).

Methods: Firstly, A549 cells were transfected with miR-126-3p to detect the role of miR-126-3p in A549 cells. Next, miR-126-3p was transfected into BMSCs, and BMSCs-derived exosomes with over-expressed miR-126-3p (Exo-miR-126-3p) were isolated through ultracentrifugation. After that, A549 cells were co-incubated with Exo-miR-126-3p to determine the effects of Exo-miR-126-3p on cell proliferation, migration, invasion, and apoptosis. Besides, the targeted relationship between miR-126-3p and protein tyrosine phosphatase non-receptor type 9 (PTPN9) was confirmed via bioinformatics analysis and dual-luciferase reporter gene analysis. Western blotting (WB) was employed to measure the expressions of PTPN9 and related proteins in A549 cells. Additionally, the effects of over-expressed miR-126-3p derived from BMSCs exosomes on tumor growth and apoptosis of NSCLC cells were analyzed in connection with lentiviral packaged miR-126-3p in vivo.

Results: Overexpressed miR-126-3p suppressed the viability, migration, and invasion of A549 cells in vitro. Based on the results of exosome content analysis, miR-126-3p could mediate the inhibitory effect of exosomes on A549 cells by negative regulation of PTPN9. Notably, over-expressed miR-126-3p derived from BMSCs inhibited the tumor growth and apoptosis in vivo.

Conclusions: Taken together, the key finding of the study indicated that over-expressed BMSCs-derived exosomal miR-126-3p can suppress the progression of NSCLC through negatively regulating PTPN9.

Despite its well known harmful effects on health, tobacco use is widespread throughout the world. Approximately one third of the global population become smokers at the age of 15 years or more. The prevalence of smoking between genders is lessening. Earlier, men used to smoke three to four times more than women globally. The nicotine content of cigarette is small (10 to 12 mg) and a smoker inhales about 1.1 to 1.8 mg of nicotine from each cigarette smoked to its entire length; this plant alkaloid stimulates the central nervous system, causes either ganglionic stimulation in low doses or ganglionic blockade in high doses, and smokers can develop a moderate to heavy physical dependence. Among other numerous substances, several are cancerogenic, and about 98 percent of lung cancer deaths are caused due to tobacco smoke. Nicotine addiction is often more severe than alcohol addiction. Smoking also may complicate anesthetic management, and passive smoking increases the rate of perioperative airway complications in the children of smokers, too. Preoperative abstinence from tobacco is required for surgical patients and it offers an opportunity for smokers to quit permanently. Physicians have an important role in helping smokers to quit tobacco or e-cigarettes, but if a doctor is a smoker himself, his antismoking influence may be deficient. Since a significant percentage of medical students are smokers, it is worth influencing them to stop the habit. The best way is to introduce tobacco modules, stimulating students to participate in anti-smoking campaigns, offer non-smoking hospitals, non-smoking university campuses, non-smoking dormitories, and to provide medical assistance to student smokers who wish to quit.

Purpose: Natural killer/T cell lymphoma (NKTCL) is a malignant condition. The molecular pathological mechanism of NKTCL has not been well studied. In this article we tried to study the role of microRNA-188-5p (miR-188-5p) in NKTCL.

Methods: The expression level of miR-188-5p and XRCC5 was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay and colony formation assay were used to assess the ability of cell proliferation. Dual luciferase reporter assay was used to examine the down-stream target of miR-188-5p. Western blotting was utilized to determine XRCC5 expression level.

Results: miR-188-5p was down-regulated in NKTCL. High expression of miR-188-5p accelerated cell proliferation. XRCC5 was one of the down-stream targets. Our data indicated that miR-188-5p suppressed NKTCL progression via regulating XRCC5 expression.

Conclusions: This research elucidated that miR-188-5p suppressed tumor progression in NKTCL by regulating XRCC5. Our data may provide more evidence in looking for novel therapeutic targets.

Purpose: Colorectal cancer represents the second most common type of cancer in Serbia. Alteration of lipid metabolism begins early, and can represent a central hallmark in cancer evolution. Fatty acids have various important functions as building components of cell membranes, as signaling molecules in immune responses and also manage the general cancer signaling network. The purpose of this study was to investigate the difference of various fatty acids content between colorectal cancer and adjacent healthy intestinal tissue in adult and aged patients of both sexes.

Methods: 52 subjects participated in this study. Healthy colon mucosa and tumor tissue samples were obtained from patients previously diagnosed with colorectal carcinoma. Simplified method of Berstad et al was used for direct transesterification of total lipids in tumor and healthy mucosa tissue samples and separations of the methyl esters was carried out using a gas chromatograph equipped with a split/splitless injector and a flame ionization detector.

Results: 18 0, 18 1 n7, 20 3, 20 4, 20 5, 22 4, 22 5 22 6, SFA, PUFA, n6, n3 and AA/EPA were significantly higher in tumor tissue. On the other hand, 18 1 n9, 18 2, 18 3 n3, MUFA, n6/n3 were significantly higher in healthy tissue.

Conclusions: Saturation index (SI) could be a valuable tool to delineate robust immune response and worse prognosis in patients with colorectal cancer. Our study demonstrated significant differences in fatty acid profiles between tumor tissue and healthy mucosa. Parameters, such as gender, age, stage and mucinous component didn't influence altered fatty acid content.

Purpose: The purpose of this study was to investigate the prognostic value,and the effect of primary tumor location on targeted therapy selection in patients with metastatic colorectal cancer (mCRC).

Methods: A total of 201 patients with de novo mCRC who received first line treatment were retrospectively analyzed. Clinicopathological features, treatment outcomes, the primary tumor surgery, metastasectomies/local therapies and survivals were evaluated in terms of both RAS mutation status and primary tumor sidedness.

Results: Tumor localization showed 140 (69.7%) patients with left-sided and 61 (30.3%) with right-sided tumors. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with right-sided tumor than those with left-sided tumors (10.1 vs 12.9 months, p=0.005; 25 vs 44.4 months, p=0.008, respectively). In addition,the median OS interval of patients receiving anti-VEGF containing regimen was better than those treated with anti-EGFR containing regimen (50.7 vs. 26.9 months, p=0.001). Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors.

Conclusions: Our results showed that primary tumor location is a prognostic factor in mCRC patients regardless of RAS status. Primary tumor location before treatment decision may be a simple indicator predicting survival and in choosing targeted agent.

Purpose: HOXD10 downregulation resulting from epigenetic changesas well as its role as a tumor suppressor have been reported in several cancers including hepatocellular carcinomas (HCCs). However, the prognostic role of HOXD10 expression in HCC tissue samples has not been evaluated.

Methods: HOXD10 expression was investigated in 278 curatively resected HCC samples using immunohistochemistry and its effectiveness in predicting patient outcome was analyzed.

Results: Low expression of HOXD10 was observed in 82.7% of HCC samples, and this was associated with increased age, large tumor size and advanced stage.HOXD10 was an independent predictive factor for early tumor recurrence at less than 2 years. Patients with low HOXD10 expression showed shorter recurrence-free survival (RFS) (p=0.024) and disease-specific survival (DSS) (p=0.016) than those with high expression. Multivariate analysis confirmed that low HOXD10 expression was an independent predictor of shorter RFS (hazard ratio 1.873, p=0.006) and DSS (hazard ratio2.504, p=0.012) than high HOXD10 expression.

Conclusions: The present study provides clinical evidence supporting the use of HOXD10 as a prognostic biomarker in curatively resected HCCs, and suggests that HOXD10 could also be a potential therapeutic target in HCC.

Purpose: The objective of the present study was to compare the efficacy of axitinib and nivolumab in metastatic renal cell carcinoma (mRCC) previously treated with targeted therapy.

Methods: A total of 79 patients were enrolled (39 patients in axitinib group, 40 patients in nivolumab group). Survival outcomes of patients, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test. The associations between potential prognostic variables and OS were evaluated in univariate and multivariate Cox regression analyses.

Results: The median PFS and OS of all cohort were 8.1 and 36.6 months, respectively. Higher PFS and OS were evaluated in axitinib group than nivolumab group (PFS: 9.4 months vs 6.3 months, p=0.386; OS: 38.2 months vs 36.6 months, p=0.671, respectively). Patients treated with axitinib had numerically higher objective response rate (ORR) and disease control rate (DCR) than those treated with nivolumab (ORR: 43.6% vs 27.6%, p=0.157, DCR: 74.4% vs 62.5%, p=0.157, respectively). Multivariate analysis revealed that the independent predictors of OS were higher tumor grade (hazard ratio [HR]: 6.178, p=0.004), worse response to axitinib and nivolumab (HR:4.902, p=0.011), the presence of lung metastasis (HR:15.637, p=0.002) and the presence of liver metastasis (HR:12.010, p=0.001).

Conclusion: Comparable survival outcomes were detected in the axitinib and nivolumab groups. However, head to head comparisons are needed to highlight the relative efficacy of these therapies in mRCC.

Purpose: At present, the global incidence of lung cancer is still high. Exploring its effective treatment is still a crucial research direction. Trefoil factor 3 (TFF3) was found to be related to the proliferation and apoptosis of many tumor cells. Therefore, this article focuses on the effect of TFF3 on SPC-A1 lung cancer cells.

Methods: The tissue samples of lung cancer patients were collected, and the expression level of TFF3 was detected by Western blot (WB) and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) techniques. After transfection technique was used to silence the expression of TFF3 in SPC-A1 cells, the proliferation activity of SPC-A1 cells was detected by CCK-8 assay and EdU staining, and the cell cycle and related factor expression levels were also detected. The apoptosis rate of SPC-A1 cells was detected by Tunel staining and flow cytometry, and the expression levels of apoptosis-related factors were also detected.

Results: TFF3 in lung cancer tissues was obviously higher than that in para-carcinoma tissue. At the same time, similar results were found in SPC-A1 lung cancer cells. CCK-8 assay and EdU staining found that silencing TFF3 gene expression can effectively inhibit the proliferation of SPC-A1 cells. Flow cytometry detection of SPC-A1 cell cycle showed that cells were blocked in G0/G1 phase, and the number of cells in S+G2/M phase was obviously reduced. Cyclin D1 expression was also obviously reduced. At the same time, silencing TFF3 gene expression can promote the increase of Bax expression and inhibit the expression of Bcl-2, thereby increasing the apoptosis rate of SPC-A1 cells. Furthermore, silencing the TFF3 gene can effectively inhibit the excessive activation of the Wnt/β-catenin pathway in SPC-A1 cells.

Conclusions: Our results show that the expression of TFF3 in lung cancer was obviously increased. Silencing TFF3 in SPC-A1 cells can inhibit the cell proliferation and promote cell apoptosis. At the same time, we confirmed that silencing TFF3 gene can inhibit the abnormal activation of Wnt/β-catenin signaling pathway in SPC-A1 cells.