Serum Fork-Head Box D3 (FOXD3) Expression Is Down-Regulated in and Associated with Diagnosis of Patients with Non-Small Cell Lung Cancer.

BACKGROUND The aim of this study was to detect the expression of fork-head box D3 (FOXD3) and investigate its diagnostic value in patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS The relative expression of FOXD3 at mRNA and protein levels was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analysis, respectively. Chi-square test was used to explore the relevance of FOXD3 expression with clinical features of NSCLC patients. A receiver operating characteristic (ROC) curve was built to estimate the diagnostic value of FOXD3 in distinguishing NSCLC patients from healthy controls. RESULTS Serum FOXD3 expression was weakly expressed in NSCLC patients compared to the controls at mRNA and protein levels (P<0.001) and low FOXD3 expression was positively correlated with TNM stage, lymph node metastasis, and differentiation. The ROC curve indicated that FOXD3 acts as a diagnostic bio-marker for NSCLC patients, with an AUC of 0.826 corresponding to a sensitivity of 77.1% and a specificity of 74.6%, and an optimal cutoff point of 2.38. CONCLUSIONS Decreased expression of serum FOXD3 was observed in NSCLC patients, and it was found to be a potential molecular marker for the diagnosis of NSCLC.

ABCE1 plays an essential role in lung cancer progression and metastasis.

ATP-binding cassette E1 (ABCE1) is a member of the ATP-binding cassette transporters and regulates a broad range of biological functions including viral infection, cell proliferation, and anti-apoptosis. We have previously shown that ABCE1 is a prognostic indicator for lung cancer, although the underlying mechanisms remain unclear. To investigate whether the ABCE1 gene contributes to the malignancy of lung tumors, we introduced ABCE1 into LTEP-a-2 lung adenocarcinoma cells. Ectopic ABCE1 expression promoted clonogenicity and anchorage-independent growth of LTEP-a-2 cells, while in a mouse xenograft tumor model, it had an augmentative effect on tumor growth and metastasis and reduced the expression of the tumor-suppressor gene growth arrest and DNA damage-inducible 45α (GADD45α). Moreover, apoptosis was not significantly influenced by ABCE1 in vitro. In summary, we have provided evidence that ABCE1 plays an essential role in the progression and metastasis of lung cancers and may represent a valuable therapeutic target for the management of lung tumor.

Bufalin Induces Programmed Necroptosis in Triple-Negative Breast Cancer Drug-Resistant Cell Lines through RIP1/ROS-Mediated Pathway.

OBJECTIVE: To explore the effect and mechanism of action of bufalin in triple-negative breast cancer (TNBC) drug-resistant cell lines. METHODS: The normal human mammary epithelial cell line, TNBC cell line, TNBC adriamycin-resistant cell line, and TNBC docetaxel-resistant cell line were treated with different doses of bufalin (0-1,000 nmol/L) at different time points (0-72 h). Propidium iodide staining, AV-FITC/PI double staining, Hoechst 33342/PI double staining and transmission electron microscopy (TEM) were used to evaluate the death patterns of the cell lines. RESULTS: Bufalin killed the TNBC cell line and its drug-resistant cell lines in a dose/time-dependent manner (all P<0.01). After treatment with bufalin for 24 h, the adriamycin-resistant cell line showed a co-existing pattern of necroptosis and apoptosis. However, at 48 h, necroptosis was the main manifestation. After treatment with bufalin, the expressions of tumor necrosis factor α, phospho-tumor necrosis factor receptor 1, phospho-receptor interacting protein 1 and c-caspase 3 increased (all P<0.01), the killing effect of bufalin could be mostly inhibited by NEC-1, and by z-VAD-fmk (both P<0.01). Besides, the intracellular reactive oxygen species (ROS) levels increased considerably (P<0.01), the antioxidant N-acetyl cysteine or Nec-1 could inhibit the increase of ROS level and the killing effect of bufalin (all P<0.01). The adriamycin-resistant cell line exhibited necroptosis characteristic after 48 h of bufalin treatment under TEM. CONCLUSIONS: Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines. This finding provides critical experimental data and theoretical basis for the clinical application of bufalin to overcome the difficulties in the treatment of TNBC.

Chest radiotherapy after left upper lobectomy may be a risk factor for thrombosis in the pulmonary vein stump.

BACKGROUND: Thrombosis in the pulmonary vein stump (PVS) is not a well-known complication after pulmonary lobectomy, but it has the potential to cause embolism to vital organs. The aim of this study was to evaluate the risk factors for thrombosis in the PVS after pulmonary lobectomy. METHODS: A total of 439 patients who underwent pulmonary lobectomy from 2008 to 2017 were retrospectively reviewed, and 412 patients were further analyzed. The state of the PVS was evaluated by chest contrast-enhanced computed tomography (CECT). Univariate analysis was performed to evaluate the potential risk factors for thrombosis in the PVS. RESULTS: Thrombosis in the PVS was detected in 6 of 412 (1.5%) patients, and 5 of them underwent left upper lobectomy (LUL) (5/100, 5.0%) (P = 0.004). In the analyses of the LUL group, postoperative chest radiotherapy was identified as a risk factor for thrombosis in the PVS (P = 0.024), and postoperative atrial fibrillation showed a tendency to be a risk factor for thrombosis (P = 0.058). CONCLUSIONS: Chest radiotherapy after LUL is a possible risk factor for thrombosis in the PVS. Periodic chest CECT is recommended after postoperative chest radiotherapy for patients after LUL.

Left superior pulmonary vein stump thrombosis and right renal infarction after left upper lobectomy: case report and literature review.

Left upper lobectomy (LUL) has been considered to have a higher risk of thrombus formation in the pulmonary vein stump (PVS) than other lobectomies. A case of thrombus formation in the PVS and right renal infarction detected by contrast-enhanced computed tomography (CECT) 12 days after LUL is presented. The thrombus in the PVS was considered to be related to the renal infarction because of the lack of other potential explanations. After intravenous heparin treatment for 1 week and continuous oral anticoagulation, the thrombus in the PVS became smaller 3 months after the operation, and it basically disappeared after 1 year. Scar formation was detected in the area of renal infarction 3 months after the operation, and no specific change was detected from then on. One should consider performing postoperative chest and abdominal CECT routinely within 1 week after LUL, and, if thrombosis is found, antithrombotic therapy might then be given.

Novel approach for predicting occult lymph node metastasis in peripheral clinical stage I lung adenocarcinoma.

BACKGROUND: Occult nodal metastasis results in a poor prognosis for lung cancer patients. The aim of this study was to develop an efficient approach for predicting occult nodal metastasis in peripheral clinical stage I lung adenocarcinoma. METHODS: Data for 237 peripheral clinical stage I lung adenocarcinoma patients who underwent complete resection were retrospectively reviewed. Univariate and multivariate analyses were performed to investigate predictors of occult nodal metastasis. Kaplan-Meier analysis was performed for survival. RESULTS: Occult nodal metastasis was detected in 26/237 (11.0%) patients. Nodule type, tumor SUVmax, whole tumor size, solid tumor size, and preoperative serum carcinoembryonic antigen (CEA) were identified as preoperative predictors of occult nodal metastasis (all P<0.05). Solid tumor size (P<0.001) and preoperative serum CEA (P=0.004) were identified as independent predictors on multivariate analysis. A prediction model was established using the independent predictors. The occult nodal metastasis rate was 2.4% with solid tumor size ≤2.3 cm (low-risk group), 17.0% with solid tumor size >2.3 cm and CEA ≤5 ng/mL (moderate-risk group), and 56.0% with solid tumor size >2.3 cm and CEA >5 ng/mL (high-risk group). The occult nodal metastasis rate was significantly higher in papillary-predominant (11.0%) and solid-predominant subtypes (28.6%; P=0.001). Patients having a micropapillary component had a significantly higher occult nodal metastasis rate (24.2%) compared with no micropapillary component (P=0.007). Histological subtype with micropapillary component and all preoperative predictors were significant prognostic factors affecting disease-free survival (DFS) (all P<0.05). CONCLUSIONS: A novel approach to predict occult nodal metastasis was developed for peripheral clinical stage I lung adenocarcinoma. It would be helpful for selecting candidates for stereotactic ablative radiotherapy (SABR) or wedge resection and mediastinoscopy or endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). Complete nodal dissection should be performed for moderate to high-risk patients or patients with poor histologic subtypes.

Comparison of perioperative and oncological outcomes between video-assisted segmentectomy and lobectomy for patients with clinical stage IA non-small cell lung cancer: a propensity score matching study.

BACKGROUND: Segmentectomy for lung cancer remains controversial because of the complexity of the procedure and concern about an increased recurrence rate. It is important to compare perioperative and oncological outcomes between segmentectomy and lobectomy. METHODS: From January 2007 to December 2016, 41 segmentectomies by video-assisted thoracic surgery (VATS) and 122 VATS lobectomies for 163 patients with clinical stage IA non-small cell lung cancer (NSCLC) were performed. Clinicopathological factors, including recurrence rate and survival rate, were compared. In order to reduce biases of outcomes, clinicopathological factors were used for propensity score matching (PSM). Then, 41 VATS segmentectomies and 41 lobectomies were selected and further analyzed. RESULTS: No significant differences were seen between the two groups in age, pulmonary function, comorbidity, operative time, blood loss, chest tube duration days, postoperative stay days, complications, histological type, and multiple primary rate. Smoking index resected number of nodes, tumor size, lymph node metastasis rate, and pathological stage were higher in the lobectomy group than in the segmentectomy group (P<0.05). In the lobectomy group, 16 patients (13.1%) had recurrence, and 2 patients (1.6%) died because of cancer progression. There were no significant differences in the recurrence rate and prognosis between the two groups. In addition, Cox regression analysis suggested that sex, lymph node metastasis, and pathology stage were associated with recurrence (P<0.05), but no factor was an independent prognostic factor. After PSM, the two groups had similar clinicopathological factors, and the type of operation still had no relationship with the recurrence rate or the death rate. CONCLUSIONS: Perioperative and oncological outcomes of VATS segmentectomy are similar to those of VATS lobectomy for patients with clinical stage IA NSCLC. VATS segmentectomy can be considered one of the surgical procedures appropriate for patients with clinical stage IA NSCLC.

Expression of ATP binding cassette E1 enhances viability and invasiveness of lung adenocarcinoma cells in vitro.

ATP binding cassette E1 (ABCE1), a member of the family of ATP binding cassette transporters, has initially emerged as an RNase L inhibitor. As a highly conserved protein, it is involved in capsid assembly and translation processes of the human immunodeficiency virus as well as in tumor development and progression. Studies have shown that ABCE1 protein was overexpressed in lung carcinoma tissues and metastatic lymph nodes compared to normal lung tissues. However, little is known about the roles of ABCE1 in lung cancer. The present study investigated the biological effects of vector-mediated ABCE1 overexpression in lung cancer cells in vitro and examined the underlying molecular mechanisms. Overexpression of ABCE1 in the LTEP­a-2 lung adenocarcinoma cell line was achieved by transfection with a plasmid containing full­length ABCE1 cDNA. The ectopic expression of ABCE1 was shown to promote the viability and invasive capacity of lung cancer cells, and to in reduce p27 expression. However, overexpression of ABCE1 did not significantly affect the cell cycle distribution. In conclusion, the present study suggested that ABCE1 promotes the growth, invasion and metastasis of lung adenocarcinoma cells and may represent a potential biomarker and therapeutic target for lung cancer.