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J BUON [JOURNAL]

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LINC00355 triggers malignant progression of hepatocellular carcinoma via the sponge effect on miR-217-5p with the involvement of the Wnt/β-catenin signaling.

Luo X, ABudureyimu M, Yang G … +6 more , Yan Z, Fu X, Lu P, Zhang D, Zhang S, Ding Z

J BUON · 2021 · PMID 34761606

PURPOSE: To uncover the biological role of LINC00355 in regulating the proliferative and apoptotic potentials in hepatocellular carcinoma (HCC), and the underlying mechanism. METHODS: LINC00355 levels in HCC tissues and... PURPOSE: To uncover the biological role of LINC00355 in regulating the proliferative and apoptotic potentials in hepatocellular carcinoma (HCC), and the underlying mechanism. METHODS: LINC00355 levels in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After knockdown of LINC00355 or miR-217-5p in Hub7 and Hep3B cells, proliferative and apoptotic potentials were assessed by cell counting kit-8 (CCK-8), colony formation assay and flow cytometry. The interaction between LINC00355 and miR-217-5p was determined by dual-luciferase reporter assay and Pearson correlation test. Western blot analysis was conducted to illustrate the regulatory effects of LINC00355 and miR-217-5p on the Wnt/β-catenin signaling. RESULTS: LINC00355 was upregulated in HCC tissues and cell lines. Knockdown of LINC00355 reduced viability in Hub7 and Hep3B cells, which was much pronounced on days 3 and 4. Clonality was attenuated by transfection of shLINC00355 as well. In addition, apoptosis rate increased by knockdown of LINC00355 in HCC cells. Protein levels of β-catenin, GSK3β, c-myc and cyclin D1 were downregulated in Hub7 and Hep3B cells transfected with shLINC00355. MiR-217-5p was the target gene binding LINC00355. It displayed exactly opposite regulations on HCC cell phenotypes and protein levels of vital genes in the Wnt/β-catenin signaling to those of LINC00355. CONCLUSIONS: LINC00355 is upregulated in HCC specimens, LINC00355 triggers proliferative rate and inhibits apoptosis in HCC cells by negatively regulating miR-217-5p and activating the Wnt/β-catenin signaling.

The Akt/GSK3β/β-catenin signaling regulated by ZCCHC14 is responsible for accelerating the proliferation of hepatocellular carcinoma.

Cui Y, Zhang J, Chen C … +3 more , Luo J, Yan H, Jiang W

J BUON · 2021 · PMID 34761605

PURPOSE: To clarify how ZCCHC14 affects the development of hepatocellular carcinoma (HCC). METHODS: Differential levels of ZCCHC14 in HCC tissues and cells were examined. Proliferative and migratory changes in HCC cells... PURPOSE: To clarify how ZCCHC14 affects the development of hepatocellular carcinoma (HCC). METHODS: Differential levels of ZCCHC14 in HCC tissues and cells were examined. Proliferative and migratory changes in HCC cells with overexpression or knockdown of ZCCHC14 were detected using 5-Ethynyl-2'- deoxyuridine (EdU) and Transwell assay, respectively. Expression changes of p-Akt/Akt, p-GSK3β/GSK3β and β-catenin in HCC cells mediated by ZCCHC14 were determined. Intervened by the p-Akt activator SC79 or overexpression of β-catenin, further validated the involvement of the Akt/GSK3β/β-catenin signaling in HCC cell phenotypes mediated by ZCCHC14. RESULTS: Upregulated ZCCHC14 in HCC accelerated in vitro proliferative potential of HCC cells. Knockdown of ZCCHC14 inactivated the Akt/GSK3β/β-catenin signaling and inhibited malignant phenotypes of HCC, which were partially reversed by SC79 induction or overexpression of β-catenin. CONCLUSIONS: By activating the Akt/GSK3β/β-catenin signaling, ZCCHC14 accelerates HCC cells proliferation.

Comparing the efficacy and safety of local-regional treatments for hepatocellular carcinoma with portal/hepatic vein tumor thrombosis in China: a network meta-analysis of randomized controlled trials.

Wu QQ, Gao H, Du SS … +5 more , Chen YX, Hu Y, Yang P, Hou JZ, Zeng ZC

J BUON · 2021 · PMID 34761604

PURPOSE: To assess the efficacy and safety of different peri-operative regimens using the network meta-analysis for hepatocellular carcinoma (HCC) with portal/hepatic vein tumor thrombosis. The interested modalities incl... PURPOSE: To assess the efficacy and safety of different peri-operative regimens using the network meta-analysis for hepatocellular carcinoma (HCC) with portal/hepatic vein tumor thrombosis. The interested modalities included neoadjuvant three-dimensional radiotherapy (3D-CRT), post-operative intensity modulated radiation therapy (IMRT), post-operative transarterial chemoembolization (TACE), 3DCRT plus TACE and surgery alone. METHODS: PubMed and Cochrane Library electronic databases were systematically searched for eligible studies published up to March 2021. Data related to treatment efficacy including overall survival (OS) and disease-free survival (DFS) were extracted and compared using a Bayesian approach. Adverse events (AEs) were assessed and compared. RESULTS: Five studies published between 2009 and 2021 were enrolled in this network meta-analysis. The comparison showed that surgery with IMRT ranks relatively higher in prolonging OS in advanced HCC patients, followed by neoadjuvant 3DCRT and surgery plus TACE. Neoadjuvant 3DCRT and postoperative IMRT appear to be better choices than 3DCRT plus TACE in terms of OS. IMRT, TACE and neoadjuvant 3DCRT group were all superior to surgery alone in terms of DFS. The rate of AEs did not differ significantly. CONCLUSIONS: Adjuvant IMRT showed more favorable treatment responses compared to other regimens in HCC patients as a peri-operative regimen.

HOXD10 expression as a prognostic factor for hepatocellular carcinoma treated with curative resection.

Park S, Choi S, Hee Koh H … +2 more , Park CK, Ha SY

J BUON · 2021 · PMID 34761603

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... 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.

Characterization of the m6A-related lncRNA signature in predicting prognosis and immune response in patients with colon cancer.

Chen S, Li X, Guo L … +5 more , Zhang J, Li L, Wang X, Zhu Y, Wang J

J BUON · 2021 · PMID 34761602

PURPOSE: Colon adenocarcinoma (COAD) is globally one of the most frequently occurring malignant tumors. The patients' 5-year survival rate with colon cancer was poor. There is a usual form of mRNA modification called N6-... PURPOSE: Colon adenocarcinoma (COAD) is globally one of the most frequently occurring malignant tumors. The patients' 5-year survival rate with colon cancer was poor. There is a usual form of mRNA modification called N6-methyl adenosine (m6A). It is adjusted by the m6A RNA methylation modulator. Nevertheless, few studies of COAD can fully discuss m6A-related lncRNAs' prognostic function. METHODS: From The Cancer Genome Atlas (TCGA) database, this study of COAD samples discussed 23 m6A regulator-related lncRNAs systemically. 2 m6A patterns with various clinical results were recognized, and a remarkable correlation between various m6A clusters and tumor immune microenvironment was discovered. RESULTS: According to prognostic analysis, cluster1 had a higher immune checkpoint programmed death-ligand 1 (PD-L1) expression and a better prognosis. A 6 m6A-related lncRNAs model was constructed through least absolute shrinkage and selection operator (LASSO), univariate, multivariate Cox regression and stratified analysis. The outcomes reported that compared with the low-risk group, high-risk groups that were based on model closely were related to poor overall survival (OS). The study ensured a risk model consisting of 6 m6A-related lncRNAs as independent prognosis predictors. For the expression differences between the two groups, Genomes Pathway Analysis, Kyoto Encyclopedia of Genes (KEGG) and Gene Ontology (GO) biological process analyses were conducted. In addition, on the basis of full analysis of OS, a nomogram based on gender, age, lncRNA feature and the stage was constructed. One year, two years, and three years are the periods when the calibration chart performed best. CONCLUSIONS: The outcomes of the study confirmed the underlying function of m6A-related lncRNAs and offered fresh perspectives to COAD prognosis.

RNF6 enhances radioresistance in colorectal cancer via activating the Wnt pathway.

Zhong X, Zhou B, Lv Z … +1 more , Liu Y

J BUON · 2021 · PMID 34761601

PURPOSE: RNF6 is verified to promote the malignant growth of colorectal cancer (CRC) and its level is linked to prognosis in CRC patients. Radioresistance is a key factor influencing prognosis in CRC. This study aimed to... PURPOSE: RNF6 is verified to promote the malignant growth of colorectal cancer (CRC) and its level is linked to prognosis in CRC patients. Radioresistance is a key factor influencing prognosis in CRC. This study aimed to uncover the potential regulation of ring finger protein 6 (RNF6) in CRC radioresistance. METHODS: RNF6 levels in radioresistant and non-radioresistant CRC patients were detected. In vitro and in vivo regulatory effects of RNF6 on radioresistant CRC cell lines and nude mice bearing radioresistant CRC were examined, respectively. The involvement of Wnt pathway in CRC radioresistance was explored by Western blot. RESULTS: RNF6 was highly expressed in radioresistant CRC species than that of non-radioresistant ones. Identically, RNF6 was upregulated in radioresistant CRC cells compared to parental cells. SW1116 cells overexpressing RNF6 were more tolerant to radiotherapy, and similar results were obtained in nude mice bearing radioresistant CRC with overexpression of RNF6. Moreover, the Wnt pathway was activated during RNF6-induced radioresistance improvement in CRC. CONCLUSIONS: RNF6 enhances radioresistance of CRC through activating the Wnt pathway.

Efficacy of endoscopic submucosal dissection in treating early colorectal cancer and precancerous lesions.

Qu L, Cheng Y

J BUON · 2021 · PMID 34761600

PURPOSE: To compare the efficacy and safety between endoscopic submucosal dissection (ESD) and conventional surgical treatment in the treatment of colorectal cancer (CRC) and the precancerous lesions. METHODS: A retrospe... PURPOSE: To compare the efficacy and safety between endoscopic submucosal dissection (ESD) and conventional surgical treatment in the treatment of colorectal cancer (CRC) and the precancerous lesions. METHODS: A retrospective analysis was performed on the clinical data of 65 patients with CRC or precancerous lesions (ESD group) and another 65 patients receiving surgical treatment at the same period (Surgery group). The surgical indicators, incidence of complications, and quality of life score were compared between the two groups, and the survival and tumor progression were followed up and recorded. RESULTS: The rate of en bloc tumor resection was 89.2% (58/65) and 100% (65/65) and the rate of tumor curative resection was 92.3% (60/65) and 100% (65/65) in ESD group and Surgery group. Moreover, ESD group had markedly shorter operation time and mean hospital stay. After treatment, ESD group had higher scores of emotional functioning, fatigue, constipation, and diarrhea symptoms and general quality of life on the European Organization for Research and Treatment of Cancer quality of life questionnaire Core 30 (EORTC QLQ-C30) than Surgery group. The follow-up results showed no statistically significant difference in the 5-year recurrence rate between ESD group and Surgery group (7.7% vs. 0%, p=0.208). CONCLUSION: ESD and surgery have similar long-term clinical efficacy in treating early CRC and precancerous lesions, but ESD is more minimally invasive and safer, and is superior in accelerating postoperative recovery and improving the overall survival of patients.

Prognostic significance of primary tumor localization in patients with metastatic colorectal cancer: Is it beneficial to select targeted treatment? Real-life experience from Turkey.

Cakan B, Acikgoz O, Bilici A … +7 more , Demir T, Basak Oven B, Hamdard J, Olmuscelik O, Olmez OF, Seker M, Yildiz O

J BUON · 2021 · PMID 34761599

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... 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.

Fatty acid in colorectal cancer in adult and aged patients of both sexes.

T Juloski J, Popovic T, Martacic JD … +5 more , V Cuk V, S Milic Perovic M, S Stankovic M, M Trbovich A, Luka SR

J BUON · 2021 · PMID 34761598

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 impor... 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.

Impact of peroxiredoxin-6 expression on colon adenocarcinoma.

Falidas E, Kitsiouli E, Tsounis D … +7 more , Kalogirou A, Tsiambas E, Tsouvelas G, Papadopoulos S, Mitsis M, Lekka M, Vlachos K

J BUON · 2021 · PMID 34761597

PURPOSE: Peroxiredoxins (Prdxs) represent a family of proteins that act as antioxidant enzymes and are involved in a variety of metabolic functions including mainly the intracellular hydrogen peroxide (H2O2) levels reduc... PURPOSE: Peroxiredoxins (Prdxs) represent a family of proteins that act as antioxidant enzymes and are involved in a variety of metabolic functions including mainly the intracellular hydrogen peroxide (H2O2) levels reduction. Especially, Prdx-6 protein encoded by the PRDX6 gene (1q25.1) regulates also phospholipid modifications and induces response to oxidative stress and injuries. Our aim was to investigate the expression of Prdx-6 in colon adenocarcinoma (CA). METHODS: A series of 30 formalin-fixed, paraffin-embedded primary CAs tissue sections were used and analyzed. Immunohistochemistry was performed using an anti-Prdx-6 antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained cells. RESULTS: Prdx-6 protein overexpression (increased immunostaining levels) was observed in 12/30 (40%) cases, whereas 18/30 (60%) CA tissues demonstrated low to moderate protein levels, respectively. Prdx-6 overall expression was strongly associated with the stage of the examined tumors (p=0.011), whereas other statistical significances were not assessed (inflammatory infiltration: p=0.364; carcinoma location: p=0.93; differentiation grade: p=0.517; tumor diameter: p=0.983; ulceration: p=0.622). CONCLUSIONS: Prdx-6 overexpression is observed in a significant subset of CAs correlating with aggressive biological behavior (advanced stage). Prdx-6 is a crucial enzyme for oxidative stress/injury endogenous cell response and should be an interesting agent as a biomarker and potential therapeutic target.

The association between post-progression survival and clinical characteristics of patients with metastatic colon cancer: A single center experience.

Engin Ozekin M, Gokyer A, Kucukarda A … +3 more , Kostek O, Issever K, Erdogan B

J BUON · 2021 · PMID 34761596

PURPOSE: In this study, we aimed to determine the factors which affect post-progression survival (PPS) and overall survival (OS) in patients with metastatic colorectal cancer. METHODS: 87 patients with metastatic colorec... PURPOSE: In this study, we aimed to determine the factors which affect post-progression survival (PPS) and overall survival (OS) in patients with metastatic colorectal cancer. METHODS: 87 patients with metastatic colorectal cancer had been followed up with palliative care due to disease progression or ECOG performance status after receiving at least two cycles of chemotherapy. PPS was estimated as the time between the last progression date and last control or death date in patients who were followed up with palliative care. RESULTS: 87 patients with metastatic colorectal cancer were included in the study. Evaluation with multivariate analysis of factors affecting PPS revealed a significantly longer PPS (10.8 weeks) in patients with ECOG score 0 or 1 than the PPS of patients with ECOG score 2-5 (3 weeks) (p=0.01). It was also found that PPS was 14.4 weeks in patients with CEA levels <5ng/ml,while it was 6.7 weeks in patients with CEA levels ≥5 ng/ml (p=0.001) and PPS was 13.7 weeks in patients with controlled disease after first-line chemotherapy while it was 8 weeks in patients with progression (p=0.03); both were statistically significant. No significant association was found between PPS and age, gender, tumor location, sites of metastasis, and RAS status. CONCLUSION: ECOG performance status score of 0-1, CEA levels below 5 ng/ml, and disease control with first-line chemotherapy are related to longer PPS in patients with metastatic colorectal cancer.

Clinical analysis of 125I seed implantation combined with epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small cell lung cancer.

Wang X, Wang D

J BUON · 2021 · PMID 34761595

PURPOSE: To explore the efficacy and safety of 125I radioactive seed implantation combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of advanced non-small cell lung can... PURPOSE: To explore the efficacy and safety of 125I radioactive seed implantation combined with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: 108 patients with EGFR mutation-positive unresectable advanced NSCLC (stage IIIB-IV) were randomly divided into 125I group (treated with 125I radioactive seed implantation combined with EGFR-TKIs, n=54) and EGFR-TKIs group (treated with EGFR-TKIs alone, n=54). The short-term efficacy and adverse reactions were analyzed and evaluated, the changes in the levels of peripheral blood T lymphocyte subsets, natural killer (NK) cells and related immune-inflammatory factors were analyzed, and the long-term survival and progression of disease were recorded. RESULTS: The objective response rate was 61.1% (33/54) and 51.9% (28/54), and the disease control rate was 88.9% (48/54) and 68.5% (37/54), respectively, in 125I group and EGFR-TKIs group. At 6 months after treatment, the levels of peripheral blood cluster of differentiation 3+ (CD3+), CD4+, CD4+/CD8+ and NK cells significantly rose in both groups compared with those before treatment (p<0.05), while the levels of CD8+, serum tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6) and IL-10 significantly declined compared with those before treatment. The 2-year overall survival (OS) rate was 53.7% (29/54) and 40.7% (22/54), and the median progression-free survival (PFS) was 14.5 months and 9.8 months, respectively, in 125I group and EGFR-TKIs group. CONCLUSIONS: 125I radioactive seed implantation combined with EGFR-TKIs is safe and effective in the treatment of advanced NSCLC, and its short-term efficacy and long-term survival rate of patients are significantly superior to those of EGFR-TKIs alone. At the same time, it can regulate the expressions of T lymphocyte subsets, NK cells and immune-inflammatory factors in patients, and improve their immune function.

EPHA5 Enhances the Stemness of Non-small cell lung cancer Cells Through Activating the Wnt Signaling Pathway.

Li J, Zhu Y

J BUON · 2021 · PMID 34761594

PURPOSE: To explore the effect of erythropoietin-producing hepatocellular receptor A5 (EPHA5) on the stemness of non-small cell lung cancer cells and its molecular mechanism. METHODS: Highly-expressed EPHA5 in NCI-H460 a... PURPOSE: To explore the effect of erythropoietin-producing hepatocellular receptor A5 (EPHA5) on the stemness of non-small cell lung cancer cells and its molecular mechanism. METHODS: Highly-expressed EPHA5 in NCI-H460 and NCI-H1229 cells was silenced. After EPHA5 silencing, the positive expression level of cluster of differentiation 133 (CD133) in NCI-H460 and NCI-H1229 cells was detected by flow cytometry, and the expression levels of stemness markers sex determining region Y-box 2 (Sox2), Nanog, Kruppel-like factor 4 (KLF4) and octamer-binding transcription factor 4 (Oct4) in cells were detected by Western blotting. RESULTS: The expression level of EPHA5 in non-small cell lung cancer H460 and H1229 cells was higher than that in A549 and SPC-A1 cells. After EPHA5 silencing, the levels of CD133 and stemness markers Sox2, Nanog, KLF4 and Oct4 in H460 and H1229 cells all declined. CCK-8 assay showed that Wnt agonists at a concentration of 2.5 and 5 μm had little effect on the proliferative activity of H460 and H1229 cells. Western blotting revealed that Wnt agonists at a concentration of 5 μm could better enhance the expression of β-catenin. After treatment with Wnt agonists, the expression of CD133 in H460 and H1229 cells with EPHA5 silencing by siRNA3 was higher than that before treatment, and the expression levels of Sox2, Nanog, KLF4 and Oct4 in the above two cells were also increased compared with those before treatment. However, the levels of the above indexes were all lower after treatment with Wnt agonists than those before silencing. CONCLUSION: Activating the Wnt signaling pathway can induce the increase in EPHA5 expression and enhance the stemness of non-small cell lung cancer cells.

Characteristics of pathogenic microbes in lung microenvironment of lung cancer patients without respiratory infection.

Zhang M, Zhang Y, Han Y … +2 more , Zhao X, Sun Y

J BUON · 2021 · PMID 34761593

PURPOSE: The characteristics of pathogenic microbes are useful for understanding the microbe-driven tumorigenesis. There is a lack of studies on the lung microecology for lung cancer (LC) patients without any respiratory... PURPOSE: The characteristics of pathogenic microbes are useful for understanding the microbe-driven tumorigenesis. There is a lack of studies on the lung microecology for lung cancer (LC) patients without any respiratory infection. In this work, we aimed to describe the profiles of pathogenic microbes in lung microenvironment of non-small cell lung cancer (NSCLC) patients using pathogen targeted sequencing and 16S rDNA sequencing. METHODS: A total of 22 NSCLC patients (13 adenocarcinomas and 9 squamous cell carcinomas) without any pulmonary infection were enrolled. Among them, we collected 15 pieces of tumor tissues, 5 pieces of peritumoral tissues, 6 blood serum samples, and 5 broncho-alveolar lavage fluid (BALF) samples. Pathogen targeted sequencingand16S rDNA sequencing was performed for microbial classification. RESULTS: The pathogen targeted sequencing results showed that 33, 14, 11, and 27 pathogenic microorganisms were detected in tumor tissues, peritumoral tissues, blood samples, and BALF, respectively. No common microorganisms were shared by four sample types. However, some common elements were shared by three sets: Streptococcus cristatus, Enterococcus, Staphylococcus haemolyticus, Corynebacterium pseudodiphtheria, Acinetobacter jungii, Haemophilus haemolyticus and Haemophilus parainfluenzae. Based on the 16S rDNA sequencing of two BALF samples, there were 104 OTUs found in one BALF sample and 127 OTUs in the other BALF sample; among them, there were 82 common ones, such as OTU1, OTU10, OTU101, OTU105, OTU106, and so on. Based on the above microbial classification and abundance, there might be enriched function in COG terms like COG1132, COG0438 and COG0745, and KEGG terms like K06147, K02029, and K09687. CONCLUSION: This study emphasizes the role of the microbiome in LC patients without respiratory infection. These potential biomarkers of LC based on the taxonomic composition of pathogenic microorganisms might have clinical application.

Circular RNA PRMT5 knockdown enhances cisplatin sensitivity and immune response in non-small cell lung cancer by regulating miR-138-5p/MYH9 axis.

Xu Y, Zhao R, Wang H … +5 more , Jiang J, Wang Z, Wang J, Zhang W, Li M

J BUON · 2021 · PMID 34761592

PURPOSE: To explore the role and molecular mechanism of circRNA protein arginine methyltransferase-5 (circ-PRMT5) in regulating cisplatin (DDP) resistance and immune response of non-small cell lung cancer (NSCLC). METHOD... PURPOSE: To explore the role and molecular mechanism of circRNA protein arginine methyltransferase-5 (circ-PRMT5) in regulating cisplatin (DDP) resistance and immune response of non-small cell lung cancer (NSCLC). METHODS: The expression of circ-PRMT5, miR-138-5p and myosin heavy chain 9 (MYH9) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, and western blot assay were utilized to evaluate DDP sensitivity. Interleukin 2 (IL-2), tumor necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β) production were measured by enzyme-linked immunosorbent assay (ELISA) to assess immune system's ability. A xenograft tumor model was established to explore the role of circ-PRMT5 in DDP resistance in vivo. The interaction between miR-138-5p and circ-PRMT5 or MYH9 was predicted by starBase and verified by dual-luciferase reporter assay. RESULTS: Circ-PRMT5 and MYH9 were upregulated and miR-138-5p was downregulated in DDP-resistant NSCLC tissues and cells. Circ-PRMT5 knockdown enhanced DDP sensitivity of NSCLC cells by inhibiting cell viability, migration and invasion and inducing apoptosis. Circ-PRMT5 knockdown also increased immune response by promoting the levels of IL-2 and TNF-a and decreasing the production of TGF-β. Moreover, circ-PRMT5 interference improved DDP sensitivity of NSCLC in vivo. MiR-138-5p was a direct target of circ-PRMT5 and its knockdown abated the effects of circ-PRMT5 downregulation on DDP resistance and immune response. CONCLUSION: Circ-PRMT5 knockdown increased DDP sensitivity and immune response of NSCLC cells by regulating miR-138-5p/MYH9 axis, hinting potential value of circ-PRMT5 in the diagnosis and treatment for NSCLC.

Trefoil factor 3 silencing can inhibit the proliferation and apoptosis of lung cancer cells.

Liu M, Xiao Y

J BUON · 2021 · PMID 34761591

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 ap... 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.

BMSCs-Derived Exosomal MiR-126-3p Inhibits the Viability of NSCLC Cells by Targeting PTPN9.

Chen J, Ding C, Yang X … +1 more , Zhao J

J BUON · 2021 · PMID 34761590

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 exosom... 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.

A cross-sectional study for assessing perceived symptoms, depression and quality of life in advanced lung cancer patients.

Lavdaniti M, Patrikou K, Prapa PM … +6 more , Vastardi M, C Fradelos E, Papathanasiou IV, Tzavella F, Alikari V, Tzavelas G

J BUON · 2021 · PMID 34761589

PURPOSE: The purpose of the present study was to assess the perceived symptoms, depression and quality of life (QoL) in advanced lung cancer patients undergoing chemotherapy. METHODS: The study was cross sectional and wa... PURPOSE: The purpose of the present study was to assess the perceived symptoms, depression and quality of life (QoL) in advanced lung cancer patients undergoing chemotherapy. METHODS: The study was cross sectional and was conducted in the oncology department of General Hospital "George Papanikolaou", Thessaloniki, Greece. The sample was convenient and consisted of 76 advanced lung cancer patients. A questionnaire including instruments such as Center for Epidemiologic Studies Depression Scale- CES-D, Revised Edmonton Symptom Assessment Scale r-ESAS, EORTC QLQ-C30 and demographic and clinical information was used to collect data. RESULTS: The most frequently observed symptoms were tiredness, shortness of breath, anxiety and well-being. The vast majority of patients (75.3%) had total score in CES-depression higher than 16. The type of residence affected ESAS emotional score (p=0.010). Gender affected the level of depression (p=0.014) and the type of lung cancer affected depression (p=0.036). The type of residence affected emotional functioning (p=0.010), the type of treatment influenced the score of global health status (p=0.007), the role functioning (p=0.032) and social functioning (p=0.024). Multivariate regression analysis was conducted to identify the predictors of overall QoL and depression. The statistically significant factors for QoL were pain (p<0.001) and tiredness (p=0.003), while the type of lung cancer (p<0.007), the type of insurance (p<0.025) and the type of treatment (p<0.041) influenced depression as well. CONCLUSIONS: Advanced lung cancer patients experienced moderate level in QoL and mild levels of symptoms. Demographic and clinical characteristics influenced depression and QoL.

Joint prediction of solitary pulmonary module malignant probability based on logistic regression and malignant tendency comprehensive score.

Zhou S, Wang Q, Tang T … +4 more , Cao M, Tan Y, Bai K, Liu W

J BUON · 2021 · PMID 34761588

PURPOSE: We analyzed the relationship between clinical data, tumor markers, chest high-resolution CT(HRCT) and pathology in patients with solitary pulmonary nodules (SPN) and explored the joint discrimination scheme to i... PURPOSE: We analyzed the relationship between clinical data, tumor markers, chest high-resolution CT(HRCT) and pathology in patients with solitary pulmonary nodules (SPN) and explored the joint discrimination scheme to improve the accuracy of noninvasive diagnosis. METHODS: 242 SPNs with the largest diameter D<2cmwere divided into training set (161 cases) and test set (81 cases). We screened the risk factors by single factor analysis. Then, we established the prediction equation model (PE model) based on logistic regression and malignant tendency comprehensive score model (MTCS model) based on the evaluation criteria of SPN. The weight of the two sub models was used to determine the joint evaluation model (JE model). RESULTS: Age, CEA content, maximum diameter, pleural adhesions, spicule sign, and ground glass component were independent factors of malignant prediction (p<0.05) recorded as x1~x6, and PE model was established as P1=ex/(1+ex),x=0.052x1+0.0327x2+0.212x3+1.849x4+ 1.066x5+1.769x6-7.582.According to the different performance of different manifestations of the corresponding score, we could get each score S of SPN. The MTCS model was S/8.5. The JE model was P=0.76P1+0.24S/8.5. The results of test set showed the AUC values of JE, PE, MTCS, Mayo, VA and Li Yun model for D≤2cm SPN were 0.930(95% CI:0.877-0.983), 0.922(95% CI:0.870-0.974), 0.900(95% CI:0.879-0.921), 0.782(95% CI:0.749-0.815), 0.744(95% CI:0.731-0.756) and 0.801(95% CI:0.739-0.863). The sensitivity of JE, PE, MTCS model were 87.2%, 79.2%, 73.3%, the specificity was 90.1%, 89.2%, 82.2%, and the accuracy was 89.9%, 85.5%, 81.2%. CONCLUSIONS: The joint evaluation model has better diagnostic efficiency and can provide reference for the diagnosis of SPN with D≤2cm.

Clinical significance of Keap1 in cervical cancer.

Wang J, Li X, Zhou Y … +1 more , Hong L

J BUON · 2021 · PMID 34761587

PURPOSE: To explore the expression of Kelch-like ECH-associated protein 1 (Keap1) and its clinical significance and function in cervical cancer (CC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) an... PURPOSE: To explore the expression of Kelch-like ECH-associated protein 1 (Keap1) and its clinical significance and function in cervical cancer (CC). METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were used to detect the expression of Keap1 in tissues from CC patients as well as CC cells and control cells in vitro. The relationship between Keap1 expression and CC clinicopathologic characteristics was statistically analyzed. Further, effects of Keap1 on the cell proliferation and apoptosis were evaluated through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and flow cytometry assay, respectively. RESULTS: Keap1 expression was downregulated in CC and the expression level of Keap1 was associated with stroma invasion, vascular invasion, parametrial invasion, lymph node metastasis and clinical stage. In in vitro study, upregulation of Keap1 in CC cells by transfection could significantly restrict cell proliferation and promote cell apoptosis. CONCLUSIONS: Keap1 was a novel factor involved in CC progression, and constituted a potential biomarker and therapeutic target for the CC patients.
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