Deguo Xu

Advanced research on vasculogenic mimicry in cancer

Vasculogenic mimicry (VM) is a brand‐new tumour vascular paradigm independent of angiogenesis that describes the specific capacity of aggressive cancer cells to form vessel‐like networks that provide adequate blood supply for tumour growth. A variety of molecule mechanisms and signal pathways participate in VM induction. Additionally, cancer stem cell and epithelial‐mesenchymal transitions are also shown to be implicated in VM formation. As a unique perfusion way, VM is associated with tumour invasion, metastasis and poor cancer patient prognosis. Due to VMs important effects on tumour progression, more VM‐related strategies are being utilized for anticancer treatment. Here, with regard to the above aspects, we make a review of advanced research on VM in cancer.

Activation of endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance of human small cell lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway

Objective This study aims to investigate the effects of endoplasmic reticulum stress (ERS) on autophagy, apoptosis and chemoresistance of human small cell lung cancer (SCLC) cells via the PI3K/AKT/mTOR signaling pathway. Results The expressions of ERS-related proteins (PEAK, eIF2α and CHOP) up-regulated, autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis-related proteins (Bax and procaspase-3) down-regulated in NCI-H446 and H69 cells after tunicamycin treatment for 24 h. Compared with the blank group, the tunicamycin, BEZ235 and tunicamycin + BEZ235 groups exhibited decreased expressions of p-PI3K, p-AKT and p-mTOR, and increased expressions of autophagy-related proteins (LC3, LC3-II and Beclin1) and apoptosis proteins (Bax and procaspase-3), and the most obvious changes were observed in the tunicamycin + BEZ235 group. Materials and Methods CCK-8 assay was applied to select the best cell line from five SCLC cell lines (NCI-H446, H69, H526, H146 and H209). Finally, NCI-H446 and H69 cells were selected for further experiments. NCI-H446/CDDP and H69/CDDP were selected and divided into the blank group, tunicamycin (an ESR inducer) group, BEZ235 (inhibitors of PI3K/AKT/mTOR pathway) group and tunicamycin + BEZ235 group. Cell apoptosis was detected by flow cytometry. Autophagy was observed by fluorescence microscopy and flow cytometry. Western blotting was used to detect the expressions of ERS-related proteins, autophagy-related proteins, apoptosis-related proteins and PI3K/AKT/mTOR pathway-related proteins. Conclusions Our findings provide evidence that the activation of ERS could promote autophagy and apoptosis and reverse chemoresistance of human SCLC cells by inhibiting the PI3K/AKT/mTOR pathway.

Effect of galectin-3 on the behavior of Eca‑109 human esophageal cancer cells.

Galectin-3, a β-galactoside-binding lectin, is a cell adhesion molecule involved in the regulation of tumor progression. However, the importance of galectin-3 in Eca-109 human esophageal cancer cells has not yet been elucidated. In the present study, a lentiviral vector was designed for overexpression of galectin-3 in Eca-109 cells following plasmid-mediated transfection (Eca-109/Gal-3 cells). A negative lentiviral vector was introduced into Eca-109 cells as a control (Eca-109/Neo cells). Western blot and reverse transcription-polymerase chain reaction analyses were used to measure the expression levels of galectin-3 protein and mRNA. The proliferation of Eca-109 cells was measured by a cell counting kit-8 assay. Eca-109 cell apoptosis was determined by Annexin V/7-amino-actinomycin double-staining. The migration and invasion capacity of Eca-109 cells was determined by a Transwell assay. A total of >98% Eca-109 cells were transfected with the lentiviral vector harboring galectin-3, and galectin-3 expression was detected in Eca-109 cells, Eca-109/Gal-3 cells and Eca-109/Neo cells. Compared with non-transfected and negative control Eca-109 cells, proliferation was increased significantly in the Eca-109/Gal-3 cells (P<0.05). Galectin-3 also significantly reduced Eca-109 cell apoptosis, compared with the two control groups (P=0.007 and P=0.04, respectively). Transwell migration and invasion assays revealed that significantly greater numbers of Eca-109/Gal-3 cells crossed the artificial basement membrane (55.4±3.9) compared with either the non-transfected or negative control Eca-109 cells (30.6±1.5 and 29±2.6 respectively, P<0.05). In conclusion, galectin-3 expression was significantly increased in transfected Eca-109 esophageal cancer cells, resulting in enhanced proliferation, migration and invasion, as well as reduced apoptosis. These data indicate that galectin-3 may be a potential molecular target in the treatment of esophageal cancer.

Elevated serum granulocyte-macrophage colony-stimulating factor levels during radiotherapy predict favorable outcomes in lung and esophageal cancer

The combination of exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) with radiotherapy (RT) has been demonstrated to strengthen the antitumor immune response. We hypothesized that the variation of GM-CSF during RT was correlated with cancer prognosis. We measured serum levels of GM-CSF and interferon-γ (IFN-γ) before and during RT in 126 unresectable lung and esophageal cancer patients and performed survival analyses. Upregulated GM-CSF levels during RT correlated with longer overall survival (OS) and progression-free survival (PFS). On the other hand, no difference in OS or PFS was seen at different IFN-γ levels. However, the “integrated factor”, computed as the combination of high pre-RT IFN-γ levels and upregulated GM-CSF, correlated with prolonged OS and PFS. Multivariate analyses revealed that GM-CSF levels and the integrated factor were both stronger independent prognostic factors than disease stage. These data demonstrate that GM-CSF levels during RT can be used as a prognostic biomarker for lung and esophageal cancer.

NOD2 maybe a biomarker for the survival of kidney cancer patients

Background Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) may play an important role in the outcome of kidney cancer patients. To explore the relationship between NOD2 and the prognosis of kidney cancer patients, a databank-based reanalysis was conducted. Materials and Methods Data related to kidney cancer patients at least with survival information, was obtained mainly from The Cancer Genome Atlas (TCGA). Some clinical data, not available online, was collected by personal email to the author. Then, we reanalyzed all the data in order to make a conclusion about the relationship between NOD2 gene and the prognosis of kidney cancer patients. Results A total of 1953 samples with NOD2 information from four databanks of The Cancer Genome Atlas (TCGA) were enrolled in this study. The results of KIPAN showed the Kaplan-Meier curve for risk groups, concordance index, and p-value of the log-rank testing equality of survival curves ( Concordance Index = 56.57, Log−Rank Equal Curves p=0.0009006, R^2 = 0.036/0.953, Risk Groups Hazard Ratio = 1.61 (conf. int. 1.21 ~ 2.13), p = 0.001005) , while a box plot across risk groups, including the p-value testing for difference using t-test (or f-test for more than two groups) was shown. There was a statistical significance for the p value of the result (p < 0.01 ). The similar results could be seen in KIRC and the fourth data (including 468 samples). Conclusions The status of NOD2 gene maybe a biomarker for the survival of kidney cancer patients.

Male breast metastases from nasopharyngeal carcinoma: A case report and literature review

Nasopharyngeal carcinoma (NPC) is known for its high rate of regional lymph node and distant metastasis. However, NPC rarely metastasizes to the breast and, to the best of our knowledge, only four well-documented cases of breast metastasis have previously been reported in the literature, all of which are female. A 49-year-old male was diagnosed with NPC and developed a right breast mass five months later. Breast fine needle aspiration confirmed an abundance of metastatic squamous cells within the thickened tissue. The current study presents the first male case of breast metastases from NPC to broaden the clinical database.

The relationship between tumor necrosis factor‑α polymorphisms and gastric cancer risk: An updated meta‑analysis

The aim of the present study was to evaluate the relationship between tumor necrosis factor-α (TNF-α) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta-analysis was performed to assess the association between TNF-α gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non-cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. TNF-α 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10–1.23)]. In analysis stratified by ethnicity, TNF-α 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02–1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79–1.18)]. The overall ORs (95% CIs) for TNF-α 857, TNF-α 1031 and TNF-α 863 were 1.13 (1.04–1.24), 0.94 (0.85–1.05) and 0.89 (0.78–1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF-α 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non-cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03–1.31)]. TNF-α 308 and TNF-α 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF-α 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF-α 1031 and TNF-α 863 were not significantly associated with gastric cancer risk.

Risk associated with central catheters for malignant tumor patients: a systematic review and meta-analysis

The risk of venous thrombosis and mortality associated with central catheter (PICC/CICC) for malignant tumor patients is not definite. So, we carried out a systematic review and meta-analysis to evaluate it. Among patients with comparing PICC with CICC, odds ratio (OR) or risk ratio (RR) was calculated with a random effect model meta-analysis. The result of the stratification analysis of 7 studies (PICC vs CICC) supported the theory that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs. 7 of 15 studies provided the information about the compared mortality rate of the patients. The result showed that CICCs were associated with a decrease in the odds ratio of thrombosis compared with PICCs (OR = 0.45, 95% CI:0.32–0.62, p < 0.0001, I2 = 0%,Tau2 = 0.00). Meta-analysis of 8 studies of 2639 patients showed that pharmacological deep vein thrombosis prophylaxis drugs could decrease the risk of mortality of malignant tumor patients with CICCs (RR = 0.58, 95% CI:0.48–0.71, Z = 5.32, p < 0.0001, I2 = 71%). We found that PICCs are associated with a raised risk of deep vein thrombosis, and pharmacological deep vein thrombosis prophylaxis drugs is a beneficial factor in decreasing the incidence of thrombosis, while warfarin may decrease the risk of mortality of malignant tumor patients with CICCs.

Clinical significance of serum soluble death receptor 5 concentration in locally advanced non‑small cell lung cancer patients

There is an urgent requirement for the identification of suitable biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). The present study aimed to measure the levels of serum soluble death receptor 5 (sDR5) in patients with locally advanced stage III NSCLC, and to evaluate its diagnostic and prognostic significance in these patients. The sDR5 concentrations were evaluated by the enzyme-linked immunosorbent assay method in 50 healthy controls and 122 patients with locally advanced stage III NSCLC [including 57 adenocarcinoma (ADC) and 65 squamous cell carcinoma (SCC) patients], before and after concurrent chemoradiotherapy. It was found that the pretreatment sDR5 levels in patients with NSCLC were higher than the sDR5 levels of healthy controls (P<0.001). However, no significant difference in the sDR5 levels was observed between the ADC and SCC subgroups (P=0.874). According to multiple clinical classifications, a significant increase in the pretreatment serum sDR5 levels could be observed in IIIB-stage patients compared with IIIA-stage patients (P=0.009). Patients with a tumor burden >3 cm had higher pretreatment sDR5 concentration than those with a tumor burden ≤3 cm (P=0.026). Additionally, T4-stage patients had significantly higher pretreatment sDR5 levels compared with those of T1-stage patients (P<0.001). There were no significant differences between pre- and post-treatment sDR5 concentrations in the total NSCLC patient group (P=0.462), ADC subgroup (P=0.066) and SCC subgroup (P=0.052). Furthermore, when patients were divided according to therapeutic response, the pretreatment sDR5 levels in the responder patients were significantly lower compared with those of the non-responders (P<0.001). Further survival analysis showed that the patients whose pretreatment sDR5 levels were ≤14 pg/ml (cutoff value, 14 pg/ml) had a longer progression-free survival (PFS) time than patients with sDR5 levels >14 pg/ml. However, no correlation was observed between the post-treatment sDR5 levels and therapeutic response or PFS time. To the best of our knowledge, the present study results provide the first evidence that the pretreatment serum levels of sDR5 may be a useful biomarker for the diagnosis, prediction and prognosis of patients with locally advanced stage III NSCLC.