BackgroundLung cancer stem cells have the ability to self-renew and are resistant to conventional chemotherapy. MicroRNAs (miRNAs) regulate and control the expression and function of many target genes; therefore, miRNA disorders are involved in the pathogenesis of human diseases, such as cancer. However, the effects of miRNA dysregulation on tumour stemness and drug resistance have not been fully elucidated. miR-181b has been reported to be a tumour suppressor miRNA and is associated with drug-resistant non-small cell lung cancer.MethodsCancer stem cell (CSC)-like properties were tested by a cell proliferation assay and flow cytometry; miR-181b expression was measured by real-time PCR; and Notch2 and related proteins were detected by Western blotting and immunohistochemistry. A mouse xenograft model was also established.ResultsIn this study, we found that ectopic miR-181b expression suppressed cancer stem cell properties and enhanced sensitivity to cisplatin (DDP) treatment by directly targeting Notch2. miR-181b could inactivate the Notch2/Hes1 signalling pathway. In addition, tumours from nude mice treated with miR-181b were significantly smaller than tumours from mice treated with control agomir. Decreased miR-181b expression and increased Notch2 expression were observed to have a significant relationship with overall survival (OS) and CSC-like properties in non-small cell lung cancer (NSCLC) patients.ConclusionsThis study elucidates an important role of miR-181b in the regulation of CSC-like properties, suggesting a potential therapeutic target for overcoming drug resistance in NSCLC.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1072-1) contains supplementary material, which is available to authorized users.
AIM:To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during threedimensional conformal radiotherapy (3D-CRT). METHODS:We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS:Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). CONCLUSION:Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT. INTRODUCTIONRadiotherapy (RT) can achieve good results in the treatment of non-small-cell lung cancer (NSCLC). The key is how to monitor the dose to critical normal tissues such as the heart, normal lung, and esophagus. Several factors can minimize the dose of RT to the esophagus, including proximity of the esophagus to midline tumors or mediastinal adenopathy, proximity of the esophagus to higher priority organs such as spinal cord and heart and relative paucity of information on the clinical and dosimetric predictors of radiation-induced esophageal injury.Clinicians familiar with RT planning are often forced to evaluate multiple plans that produce equivalent coverage of the target with variable sparing of critical structures. By our experience, the esophageal dose is not critically considered because the clinical and dosimetric variables predicting esophageal injury are not well characterized. The purpose of this investigation was to analyze the incidence of acute and late grade 3-5 esophageal injury in patients with NSCLC during three-dimensional conformal radiotherapy (3D-CRT) combined with or without chemotherapy (sequential or concurrent).
14-3-3ζ is involved in tumor cell growth and apoptosis. However, the mechanism of 14-3-3ζ in lung squamous cell carcinoma (SCC) metastasis has not been illuminated. In our studies, we found that the expression of 14-3-3ζ was highly expressed in lung SCC compared to normal lung tissues. High expression of 14-3-3ζ was associated with pTNM stage (p<0.05) and lymph node metastasis (p<0.05). Furthermore, the expression of 14-3-3ζ protein was associated with high levels of TGFβR1 protein (p=0.005), and pSMAD3 (p=0.033). Lung SCC patients with high 14-3-3ζ expression have significantly shorter OS and DFS compared to patients with low 14-3-3ζ expression. Additionally, 14-3-3ζ knockdown inhibited cell proliferation, migratory and invasive properties of human lung SCC cells. TGFβR1 was involved in 14-3-3ζ-mediated cell proliferation and metastasis of lung SCC cells. Additionally, sh-14-3-3ζ can suppress tumor growth and metastasis in vivo. Thus, these data provide the evidence that 14-3-3ζ promote tumor metastasis and might be a prognostic biomarker and target for therapeutic strategy in lung SCC.
This study explores the effect of preoperative radiotherapy combined with FOLFOX chemotherapy on patients with locally advanced colon cancer (LACC). Data of 102 patients with LACC were retrospectively analyzed. All received surgical resection plus postoperative FOLFOX chemotherapy; whereas 58 patients underwent preoperative radiotherapy combined with FOLFOX chemotherapy (CRT group, combined with radiotherapy treatment group), 44 patients did not undergo radiotherapy (non-CRT group). Short-and long-term effects as well as operative complications were compared. The optical density values of the caudal-related homeobox transcription factor 2 and inhibitor of growth 4 in lesions, and malignant molecules including vascular endothelial growth factor and cathepsin-D in serum were compared. The CRT group showed higher total pathological complete tumor response rate and resection rate, and lower incidence of incisional infection than the non-CRT group (all P < 0.05). The CRT group was significantly better in the three-year disease-free survival than the non-CRT group ( P < 0.05), but slightly better in the three-year overall survival and disease-free survival in the first, second, and third years ( P > 0.05). The optical density values of the caudal-related homeobox transcription factor 2 and inhibitor of growth 4 were higher than those in the non-CRT group (both P < 0.05). The levels of serum vascular endothelial growth factor and cathepsin-D in the CRT group were lower than those in the non-CRT group (both P < 0.05). Preoperative radiotherapy combined with FOLFOX chemotherapy can improve the resection rate and the pathological complete response rate in LACC surgery, and improve the survival time and the disease-free survival condition.
In recent years, an increasing number of studies have reported that long noncoding RNAs (lncRNAs) play crucial roles in breast cancer (BC) progression and metastasis. Another study group of our research center reported that lncRNA HCG18 was one of the 30 upregulated lncRNAs in BC tissues compared with normal tissues in The Cancer Genome Atlas database. However, the exact biological roles of HCG18 in BC remain unclear. In this study, we demonstrated that HCG18 is significantly upregulated in BC tissues and cells and that BC patients with high HCG18 expression tend to have poor prognosis. In vitro assays indicated that HCG18 promotes BC cell proliferation and invasion and endows BC cells with cancer stemness properties. In vivo assays revealed that reducing HCG18 expression in the BC cell line MDA-MB-231 markedly decreased tumor growth and lung metastasis in xenograft mouse models. In terms of mechanism, we found that HCG18 positively regulated the expression of BC-related ubiquitin-conjugating enzyme E2O (UBE2O) by sponging miR-103a-3p, and our previous research verified that UBE2O could promote the malignant phenotypes of BC cells through the UBE2O/AMPKα2/mTORC1 axis. Furthermore, as a downstream target of the HCG18/miR-103a-3p/UBE2O/mTORC1 axis, hypoxia-inducible factor 1α transcriptionally promoted HCG18 expression and then formed a positive feedback loop in BC. Taken together, these results confirm that HCG18 plays an oncogenic role in BC and might serve as a prognostic biomarker and a potential therapeutic target for BC treatment.
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