CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression.

Recently, circular RNAs (circRNAs) attract much attention due to their potential vital functions in multiple human diseases, including cancer. circ-BANP has been reported to modulate colorectal cancer growth. Nevertheless, the relationship between circ-BANP and lung cancer requires to be investigated. In this study, we found circ-BANP was overexpressed in lung cancer tissues. Higher circ-BANP expression was associated with lower survival rate. Moreover, silencing circ-BANP markedly inhibited proliferation, migration and invasion of lung cancer cells in vitro and impaired tumor propagation in vivo. In mechanism, circ-BANP was identified as the sponge of miR-503 while miR-503 targets LARP1. Circ-BANP-induced inhibition of miR-503 led to increased expression of LARP1 in lung cancer. Finally, rescue assays indicated that LARP1 restoration partially reversed the effects of circ-BANP knockdown in lung cancer. In sum, our study illustrated that circ-BANP-mediated miR-503/LARP1 signaling promoted lung cancer growth, migration and invasion, providing a novel insight on the mechanism underlying lung cancer progression.

Upregulation of miR-24 promotes cell proliferation by targeting NAIF1 in non-small cell lung cancer.

Recent studies have implied that aberration of miR-24 is linked to various human cancers. However, its role in non-small cell lung cancer (NSCLC) remains obscure. Here, we found that miR-24 was significantly upregulated in NSCLC tissues and patients' serum. High expression of miR-24 in patients' serum was independently correlated with a shorter overall survival of NSCLC patients. Depletion of miR-24 inhibited cell proliferation and anchorage-independent survival ability in lung cancer cell lines and reduced tumor formation ability in nude mice. Nuclear apoptosis-inducing factor 1 (NAIF1) was identified to be a functional target of miR-24 in the human lung. Next, we observed that the NAIF1 mRNA expression level in NSCLC tissues was suppressed in comparison to that in adjacent normal tissues. Restoration of NAIF1 in lung cancer cell inhibited cell proliferation and anchorage-independent survival ability, which were found to be similar with those from transfecting a miR-24 inhibitor into lung cancer cells. In conclusion, our study demonstrated that miR-24 was upregulated in NSCLC, and suppressing the expression of miR-24 inhibited tumor characteristics. MiR-24 acted as an oncomir, at least partially through regulation of its functional target NAIF1 in NSCLC. MiR-24 may serve as a novel potential biomarker for NSCLC diagnosis and prognosis.

Fast-track surgery improves postoperative clinical recovery and reduces postoperative insulin resistance after esophagectomy for esophageal cancer.

PURPOSE: This study aims to investigate the influence of fast-track surgery (FTS) on insulin resistance indicators in a prospective randomized, controlled clinical trial in esophageal cancer patients. METHODS: Between November 2009 and March 2011, 34 patients underwent the FTS pathway, and 34 patients underwent the conventional pathway after esophagectomy in our department. The times to postoperative flatus and defecation, duration of postoperative hospital stay, hospitalization expenditures, and postoperative complications were recorded. Insulin resistance indicators were measured before operation as well as on the 1st, 3rd, and 7th postoperative days (PODs), including serum levels of fasting blood glucose (FBG), fasting insulin (FINS), interleukin-6 (IL-6), and C-reactive protein (CRP) in patients of both groups. The insulin resistance index (homeostasis model assessment of insulin resistance (HOMA-IR)) was calculated at each time point. RESULTS: We found a significantly shorter postoperative hospital stay and faster return of gastrointestinal function in patients who underwent FTS (P < 0.01). In addition, the total hospitalization expenditure was significantly lower in the FTS group (P < 0.01). The preoperative insulin resistance indicators showed no significant differences between the two groups. On PODs 1 and 3, the levels of log-HOMA-IR, FINS, IL-6, and CRP in the FTS group were significantly lower than those in the control group (all P < 0.05). On POD 7, the CRP level in the FTS group was significantly lower than that in the control group (P < 0.05). CONCLUSIONS: FTS promotes early recovery of gastrointestinal function and reduces stress reaction and postoperative insulin resistance after esophagectomy for esophageal cancer.

Fast-track rehabilitation program and conventional care after esophagectomy: a retrospective controlled cohort study.

PURPOSE: The purpose of this article is to evaluate fast-track rehabilitation program and conventional care after esophagectomy using a retrospective controlled cohort study in esophageal cancer patients. METHODS: Fifty-five patients underwent fast-track rehabilitation program and 57 patients underwent conventional care after esophagectomy. Fast-track rehabilitation program was performed to patients who have early movement, epidural analgesia control, fluid infusion volume control and enteral nutrition for early discharge. The other 57 patients underwent conventional care after esophagectomy. The average of hospital stay and complications were calculated in the patients between the two groups. RESULTS: The median length of hospital stay in the patients was significantly shorter after fast-track rehabilitation program than after conventional care (7.7 vs 14.8 day, P < 0.01). The percentage of patients who developed complications was significantly lower 30 day after fast-track rehabilitation program than after conventional care (29.1 vs 47.4%, P < 0.05). 87.3% in patients of the fast-track rehabilitation program group and 54.4% in those of the conventional care group reported excellent to very good satisfaction with their pain control (P = 0.000). CONCLUSIONS: The fast-track rehabilitation program results in fewer complications, less postoperative pain, a reduction in the hospital length of stay, and quicker return to work and normal activities after esophagectomy.

Robot-assisted resection of multiple lung nodules through combination of intercostal incisions and a subxiphoid incision as a utility port.

INTRODUCTION: Robotic-assisted thoracic surgery (RATS) via subxiphoid incision may be superior in resection of multiple lung nodules. METHODS: Outcomes of robot-assisted one-stage bilateral lobectomy or segmentectomy via intercostal and subxiphoid incisions for multiple ground-glass opacities were analysed. RESULTS: Total 36 cases were analysed in this study. Thirteen cases had bilateral lobectomy + segmentectomy, 15 cases underwent bilateral segmentectomies, and 8 cases underwent lobectomy + segmentectomy + wedge resection. The average intraoperative blood loss was 110.2 ± 57.8 mL, operation time was 154 ± 64.2 min, thoracic draining time was 2.6 ± 3.2 days, and postoperative hospital stay was 4.8 ± 3.3 days. Three patients had atrial fibrillation and 3 patients had continuous air leakage for over 3 days, but there was no death or postoperative pain. CONCLUSION: Robot-assisted one-stage bilateral resection of multiple lung nodules through combination of intercostal and subxiphoid incision as a utility port is safe and reliable.

Identification of lymph node metastasis-related genes and patterns of immune infiltration in colon adenocarcinoma.

Backgrounds: Colon adenocarcinoma(COAD) is one of the most common tumors of the digestive tract. Lymph node metastasis (LNM) is a well-established prognostic factor for COAD. The mechanism of COAD lymph node metastasis in immunology remains unknown. The identification of LNM-related biomarkers of COAD could help in its treatment. Thus, the current study was aimed to identify key genes and construct a prognostic signature. Methods: Gene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes were calculated by using R software. GO functional and KEGG pathway enrichment analysis were processed. The CIBERSORT algorithm was used to assess immune cell infiltration. STRING database was used to screen key genes and constructed a protein-protein interaction network (PPI network). The LASSO-Cox regression analysis was performed based on the components of the PPI network. The correlation analysis between LNM-related signature and immune infiltrating cells was then investigated. TISIDB was used to explore the correlation between the abundance of immunomodulators and the expression of the inquired gene. Results: In total, 394 differentially expressed genes were identified. After constructing and analyzing the PPI network, 180 genes were entered into the LASSO-Cox regression model, constructing a gene signature. Five genes(PMCH, LRP2, NAT1, NKAIN4, and CD1B) were identified as LNM-related genes of clinical value. Correlation analysis revealed that LRP2 and T follicular helper cells (R=0.34, P=0.0019) and NKAIN4 and T follicular helper cells (R=0.23, P=0.041) had significant correlations. Immunologic analysis revealed that LRP2 and NKAIN4 are potential coregulators of immune checkpoints in COAD. Conclusion: In general, this study revealed the key genes related to lymph node metastasis and prognostic signature. Several potential mechanisms and therapeutic and prognostic targets of lymph node metastasis were also demonstrated in COAD.

Differential Physiological Responses to Salt Stress between Salt-Sensitive and Salt-Tolerant japonica Rice Cultivars at the Post-Germination and Seedling Stages.

Soil salinity is a key source of abiotic stress in the cultivation of rice. In this study, two currently cultivated japonica rice species-Zhegeng 78 (salt-tolerant) and Zhegeng 99 (salt-sensitive)-with similar backgrounds were identified and used to investigate their differential responses to salt stress at the post-germination and seedling stages. Quantitative RT-PCR analysis demonstrated that the expression of OsSOS1, OsHAK1, and OsHAK5 at the post-germination stage, and the expression of OsHKT1,1, OsHTK2,1, and OsHAK1 at the seedling stage, were significantly higher in the salt-tolerant Zhegeng 78 compared with those of the salt-sensitive Zhegeng 99 under salt stress. The significantly lower Na+ net uptake rate at the post-germination and higher K+ net uptake rates at the post-germination and seedling stages were observed in the salt-tolerant Zhegeng 78 compared with those of the salt-sensitive Zhegeng 99 under salt stress. Significantly higher activity of peroxidase (POD) and the lower hydrogen peroxide (H2O2) accumulation were observed in the salt-tolerant Zhegeng 78 compared with those of salt-sensitive Zhegeng 99 under salt stress at the seeding stage. The salt-tolerant Zhegeng 78 might be valuable in future cultivation in salinity soils.

The level of serum carcinoembryonic antigen is a surrogate marker for the efficacy of EGFR-TKIs but is not an indication of acquired resistance to EGFR-TKIs in NSCLC patients with EGFR mutationsm.

The aim of the present study was to define the relationship between carcinoembryonic antigen (CEA) and survival in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and to investigate whether the level of serum CEA is related to the mechanism for acquisition of resistance to EGFR-TKIs. A total of 100 patients with advanced NSCLC (stage IIIB or stage IV) and harboring EGFR mutations were included. All patients received erlotinib or gefitinib treatment. The correlation between CEA serum level and clinical benefit from erlotinib or gefitinib treatment was analyzed. Patients were appraised by a review of data from a prospective re-biopsy protocol for lung cancer patients with an EGFR-mutated phenotype with acquired resistance to EGFR-TKI therapy. Of 100 patients, 49 and 21 patients carried high and low level of CEA, respectively; 30 carried normal CEA. Median progression-free survival was 6.4 and 4.5 months in patients with high and low level of CEA, respectively (P=0.027). Median PFS of patients in low-CEA group longer than that of those with normal level of tumors (3.0 months; P=0.002). The difference between groups L and N was not significant regarding objective response rate and overall survival. No significant difference was found in three groups of acquired resistance to EGFR-TKIs. The relative CEA level could predict benefit of EGFR-TKI therapy in advanced NSCLC, but could not predict acquired resistance to EGFR-TKIs.

IL-6 mediates the signal pathway of JAK-STAT3-VEGF-C promoting growth, invasion and lymphangiogenesis in gastric cancer.

Gastric cancer shows the highest invasive and metastasis features, especially lymph metastasis, which is closely associated with poor prognosis of gastric cancer. Although there is evidence that interleukin-6 (IL-6) can promote gastric cancer progression, the underlying specific mechanisms and the mechanisms of gastric cancer lymphangiogenesis are largely unknown. In the present study, we explore whether IL-6 could promote the proliferation and invasion activity of gastric cancer cells, and whether IL-6 mediating VEGF-C production affected the lymphangiogenesis in gastric cancer cells. Our results revealed that IL-6 and its receptors (IL-6 and gp130) are broadly expressed in various gastric cancer cell lines including SGC-7901, MGC, MKN-28 and AGS. Exogenous IL-6 increased the ability of gastric cancer cell proliferation and invasion, which could be weakened by AG490. in addition, exogenous IL-6 promoted the VEGF-C production of gastric cancer cells and the lymphangiogenesis of HDLECs. As we expected, AG490 was able to reduce these effects. Western blot analysis showed that IL-6 increased JKA, STAT3, p-STAT3 and VEGF-C protein levels in the gastric cancer cells. However, the JKA, STAT3, p-STAT3 and VEGF-C protein expression levels were inhibited by AG490. Our data suggested that IL-6 mediates the singnal pathway of JAK-STAT3-VEGF-C promoting the growth, invasion and lymphangiogenesis in gastric cancer. Thus, IL-6 and its related signal pathways may be a promising target for treatment of gastric cancer growth and lymphangiogenesis.

[Effect of early enteral nutrition on immune response and clinical outcomes after esophageal cancer surgery].

OBJECTIVE: To evaluate the effect of early enteral nutrition(EEN) on immune response and clinical outcomes after esophageal cancer operation. METHODS: Sixty patients with esophageal cancer undergoing radical operation between March 2010 and July 2011 were randomly divided into two groups using envelope method: EEN group(n=30, administration of water and enteral nutrition early after operation) and TPN group(n=30, administration of total parenteral nutrition). Two groups both received 7-day nutrition support. Immune indexes(CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+)) and serum nutritional indexes(albumin, pre-albumin, transferrin) were measured before operation and 1-, 3-, and 7-day after operation. The time to first flatus, length of postoperative hospital stay, total hospitalization cost, and postoperative complication were recorded. RESULTS: As compared to TPN group, the time to first flatus was significantly shorter in EEN group[(66.5±7.3) h vs. (75.1±6.8) h, P<0.01], as was hospital stay[(7.8±1.1) d vs. (9.3±1.3) d, P<0.01]. Total hospitalization cost[(36 210±3810) yuan vs. (39 731±4013) yuan, P<0.01] was lower in EEN group as compared to TPN group. There was no significant difference in postoperative complication rate between the two groups[13.3%(3/30) vs. 20.0%(6/30), P>0.05]. The levels of CD3(+), CD4(+), CD4(+)/CD8(+), albumin, prealbumin and transferrin were significantly higher in EEN group as compared to TPN group on postoperative day 3 and 7(all P<0.05), while CD8(+) was significantly lower in EEN group(P<0.05). CONCLUSION: EEN can promote early recovery of gastrointestinal function, improve nutritional and immune function, and therefore lead to fast postoperative recovery in esophageal cancer patients.

[Mechanisms of EGF regulation of COX-2 through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells].

BACKGROUND: It has been proved that cyclooxygenase-2 (COX-2) is a key factor in lung cancer oncogenesis. COX-2 can be induced by a number of cytokines and growth factors and can be regulated by the JAK/STAT signaling pathway. Inhibiting the expression of COX-2 can prevent the development of lung cancer. The aim fo this study is to investigate whether the epidermal growth factor (EGF) can stimulate the signal transducers and activators of transcription 5 (STAT5) as well as to discover the effects of the STAT5 signaling pathway on the COX-2 in human lung adenocarcinoma A549 cells. METHODS: The phenomenon of STAT5 activation stimulated by the EGF was assayed through immunofluorescence and Western blot. The adenovirus containing the wild-type (WT)-STAT5 (AdWT-STAT5) plasmid, dominant-negative (DN)-STAT5 (Ad-CMV5Stat5aΔ740) plasmid, and STAT5 siRNA were transfected into A549 cells. The latter two groups were stimulated using EGF. Reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of COX-2. RESULTS: STAT5 was not activated in A549 cells in vitro. EGF stimulation significantly increased the level of the p-STAT5 protein and induces the shuttling of p-STAT5 from the cytoplasm into the nucleus. STAT5 activation was crucial for the COX-2 expression induced by the EGF. STAT5 was required for COX-2 expression, but can mediated the effects of the COX-2 expression through pathways that were independent of transcriptional activation. CONCLUSIONS: COX-2 expression is dependent on STAT5 phosphorylation. A second pathway does not require STAT5 phosphorylation.

Fluorescence in situ hybridization as adjunct to cytology improves the diagnosis and directs estimation of prognosis of malignant pleural effusions.

BACKGROUND: The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity and specificity. The aim of this study was to investigate the value of fluorescence in situ hybridization (FISH) as adjuncts to conventional cytologic examination in patients with malignant pleural effusions. METHODS: We conducted a retrospective cohort study of 93 inpatients with pleural effusions (72 malignant pleural effusions metastatic from 11 different organs and 21 benign) over 23 months. All the patients came from Chinese northeast areas. Aspirated pleural fluid underwent cytologic examination and fluorescence in situ hybridization (FISH) for aneuploidy. We used FISH in single-colour or if appropriate in dual-colour evaluation to detect chromosomal aberrations (chromosomes 7, 11, and 17) in effusion cells as markers of malignancy, to raise the diagnostic yield and identified the efficiency by diagnostic biopsy. Predominant cytogenetic anomalies and patterns of intratumor cytogenetic heterogeneity were brought in relation to overall survival rate. RESULTS: Cytology alone confirmed malignant pleural effusions in 45 of 72 patients (sensitivity 63%), whereas FISH alone positively identified 48 of 72 patients (sensitivity 67%). Both tests had high specificity in predicting benign effusions. If cytology and FISH were considered together, they exhibited 88% sensitivity and 94.5% specificity in discriminating benign and malignant effusions. Combined, the two assays were more sensitive than either test alone. Although the positive predictive value of each test was 94.5%, the negative predictive value of cytology and FISH combined was 78%, better than 47% and 44% for FISH and cytology alone, respectively. There was a significantly prolonged survival rate for patients with aneuploidy for chromosome 17. CONCLUSIONS: FISH in combination with conventional cytology is a highly sensitive and specific diagnostic tool for detecting malignant cells in pleural effusions . The high sensitivity and specificity may be associated with geographic area and race. Simple numeric FISH anomalies may be prognostic.

EGF stimulates cyclooxygenase-2 expression through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells.

The epidermal growth factor receptor (EGFR) can be activated by several growth factors within the tumor microenvironment, and it can activate several signaling pathways. For tumor development, these EGFR-related signaling pathways may converge on several common nuclear transcription factors, one such transcription factor being STAT5. STAT5 plays an important role in the oncogenic signal transduction pathway in non-small cell lung cancer. In this study, we examined whether the epidermal growth factor (EGF) can stimulate cyclooxygenase-2 (COX-2) expression in human lung adeno-carcinoma A549 cells transfected with or without STAT5 siRNA or dominant-negative (DN)-STAT5, and identified the pathways involved in this response. We found that STAT5 siRNA significantly reduced EGF-induced COX-2 expression, and STAT5 phosphorylation. STAT5 phosphorylation predominantly mediates EGF-induced COX-2 promoter activity. STAT5 siRNA was found to inhibit COX-2 expression in resting A549 cells despite the absence of detectable activated phosphorylated STAT5. Using an adenoviral system, we expressed DN-STAT5 in human lung adenocarcinoma A549 cells in order to broaden the investigation and to determine the role of STAT5 in EGF-mediated COX-2 gene expression. The overexpression of DN-STAT5 significantly inhibited EGF-induced COX-2 expression, and we found that EGF induced the tyrosine phosphorylation of STAT5 and up- regulated COX-2 expression. DN-STAT5 also blocked COX-2 promoter activity. Our results demonstrate that EGF stimulates COX-2 expression in human lung adenocarcinoma A549 cells via the activation of the STAT5 pathway and that COX-2 expression may be independent of phosphorylated STAT5 in A549 cells in vitro.