Promotion of non-small cell lung cancer tumor growth by FHL2 via inducing angiogenesis and vascular permeability.

Background: Antiangiogenetic therapy is one of the effective strategies for non-small cell lung cancer (NSCLC) treatment. Four-and-a-half LIM-domain protein 2 (FHL2) serves as a key function in cell growth and metastasis of multiple cancers, but the role of FHL2 in NSCLC angiogenesis has not been intensely examined. Methods: FHL2 expression in NSCLC tissues and cell lines and its correlation with patients prognosis were investigated by using The Cancer Genome Atlas (TCGA) database and quantitative polymerase chain reaction (qPCR). Cell Counting Kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, and a xenograft model were used to investigate the effects of FHL2 on NSCLC progression in vitro and in vivo. CCK-8, wound-healing, Transwell invasion, tube formation, and permeability assays were performed to determine the roles of FHL2 in angiogenesis and vascular permeability. Vascular endothelial growth factor A (VEGFA) enzyme-linked immunosorbent assay (ELISA) assay, Western blot analysis, and MK-2206 were used to investigate the specific mechanism mediated by FHL2. Results: We demonstrated that FHL2 was significantly upregulated in NSCLC tissues and cell lines and was associated with poor prognosis. FHL2 overexpression enhanced the cell viability of NSCLC cells, as well as the proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, we determined that FHL2 activated the AKT-mTOR signaling pathway in HUVECs by promoting VEGFA secretion from NSCLC cells, thereby inducing angiogenesis and vascular leakiness. We further confirmed that FHL2 also promoted NSCLC tumor growth in vivo. Conclusions: Our study revealed the role of FHL2 in NSCLC and the mechanism by which FHL2 promotes NSCLC tumorigenesis, providing novel insights into targeted therapy for NSCLC.

Modified surgical incision suturing technique in uniportal video-assisted thoracoscopic pulmonary resection.

Background: In recent years, single-hole thoracoscopic surgery technology is widely used in major medical centers and chest-specialized hospitals for the treatment of lung diseases. However, the single-hole minimally invasive surgery method focuses on one incision, and all surgical instruments need to pass through the same hole, resulting in repeated extrusion and tissue damage of the surgical incision. Therefore, we have improved the suture method of conventional surgical incision in order to reduce the probability of wound infection and dehiscence, promote early healing, and reduce the severity of postoperative wound scar, thereby enhancing the postoperative rapid recovery of patients. The purpose of this study is to explore the clinical efficacy of a modified surgical incision suture technique applied to uniportal thoracoscopic pulmonary resection. Methods: This study retrospectively analyzed 151 patients who were admitted to the Department of Thoracic Surgery and underwent pulmonary resection from January 2019 to October 2021 in the North District of Suzhou Municipal Hospital. The patients were divided into two groups according to the different surgical incision suture methods: a modified group and a conventional group. The postoperative general clinical indexes, incision infection rate, secondary suture rate, postoperative incision pain score, and the severity of postoperative incision scar were compared and analyzed between the two groups. Results: There were no statistically significant differences between the two groups in terms of chest tube duration or postoperative drainage and postoperative incision pain scores; the incision infection rate (1.3% vs. 6.7%, P<0.05), secondary suture rate (2.6% vs. 9.4%, P<0.05), and postoperative scar score (4.853 vs. 5.543, P=0.03) were better in the modified group than in the conventional group, and the differences between the two groups were statistically significant. Conclusions: Our modified suture method reduces the chance of infection and splitting and the severity of postoperative incision scar formation, promoting early healing. It can be safely and effectively applied to the incision suture of uniportal thoracoscopic pulmonary resection, enhancing the rapid postoperative recovery of patients.

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer.

Background: The incidence and mortality of non-small cell lung cancer (NSCLC) are extremely high. Previous research has confirmed that the signal transducer and activator of the transcription 3 (STAT3) protein critically participate in the tumorigenesis of NSCLC. Mebendazole (MBZ) has exerts a larger number of pharmacological activities and has anticancer effects in lung cancer, but its mechanism of action remains unclear. This study thus aimed to clarify the impacts of MBZ on NSCLC cell. Methods: Cell proliferation, migration, and apoptosis were investigated via cell counting kit 8 (CCK-8) assay, Transwell assay, colony formation assay, wound-healing assay, and flow cytometry. Reactive oxygen species (ROS) were detected with a multifunctional microplate reader. Markers of cell migration and apoptosis were detected with Western blotting. The transcriptional activity of STAT3 was detected via luciferase assay. ROS scavenger N-acetylcysteine (NAC) was used to determine the effect of MBZ on NSCLC via ROS-regulated STAT3 inactivation and apoptosis. A xenograft model was constructed in vivo to investigate the role of MBZ in NSCLC tumor growth. Results: The findings demonstrated that MBZ inhibited NSCLC cell proliferation and migration while promoting apoptosis through triggering ROS generation. In addition, the Janus kinase 2 (JAK2)-STAT3 signaling pathway was abrogated with the treatment of MBZ. NAC could distinctly weaken MBZ-induced apoptosis and STAT3 inactivation. Moreover, MBZ inhibited the tumor growth of NSCLC in vivo. Conclusions: In summary, MBZ inhibited NSCLC cell viability and migration by inducing cell apoptosis via the ROS-JAK2-STAT3 signaling pathway. These data provide a theoretical basis for the use of MBZ in treating NSCLC.

A Rare Case of an Adult Pregnant Patient with the Left Coronary Artery Originating from the Pulmonary Artery: Successful Management and Healthy Maternal-Fetal Outcome.

An anomalous left coronary artery originating from the pulmonary artery (ALCAPA) refers to the abnormal origin of the left coronary artery either from the main pulmonary artery, pulmonary artery sinus, or the left and right pulmonary arteries, with the main pulmonary artery or pulmonary artery sinus being the most common sites. If not diagnosed and treated promptly, this condition can result in death within the first year of life in 90% of patients. Asymptomatic children can survive into adulthood, but they are at a high risk of sudden death. In this article, we report a case of a 24-year-old pregnant woman who was diagnosed with ALCAPA during prenatal examination. The pregnancy was successfully maintained until 36 weeks, after which a cesarean section was performed. The patient was then admitted to the cardiac surgery department to improve cardiac function, and six weeks later, a successful left coronary artery transplantation was performed. The patient was discharged and followed up for three months, during which her condition remained stable.

FBXW7 loss of function promotes esophageal squamous cell carcinoma progression via elevating MAP4 and ERK phosphorylation.

BACKGROUND: Increasing evidence suggests that FBXW7 has a high frequency of mutations in esophageal squamous cell carcinoma (ESCC). However, the function of FBXW7, especially the mutations, is not clear. This study was designed to investigate the functional significance of FBXW7 loss of function and underlying mechanism in ESCC. METHODS: Immunofluorescence was applied to clarify the localization and main isoform of FBXW7 in ESCC cells. Sanger sequencing were performed to explore mutations of FBXW7 in ESCC tissues. Proliferation, colony, invasion and migration assays were performed to examine the functional roles of FBXW7 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, GST-pulldown, LC-MS/MS and co-immunoprecipitation assay were used to explore the molecular mechanism underlying the actions of FBXW7 functional inactivation in ESCC cells. Immunohistochemical staining were used to explore the expression of FBXW7 and MAP4 in ESCC tissues. RESULTS: The main FBXW7 isoform in ESCC cells was the ß transcript in the cytoplasm. Functional inactivation of FBXW7 led to activation of the MAPK signaling pathway and upregulation of the downstream MMP3 and VEGFA, which enhanced tumor proliferation cell invasion and migration. Among the five mutation forms screened, S327X (X means truncated mutation) had an effect similar to the FBXW7 deficiency and led to the inactivation of FBXW7 in ESCC cells. Three other point mutations, S382F, D400N and R425C, attenuated but did not eliminate FBXW7 function. The other truncating mutation, S598X, which was located outside of the WD40 domain, revealed a tiny attenuation of FBXW7 in ESCC cells. Notably, MAP4 was identified as a potential target of FBXW7. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system. Immunohistochemical staining indicated that FBXW7 loss of function was associated with tumor stage and shorter survival of patients with ESCC. Univariate and multivariate Cox proportional hazards regression analyses showed that high FBXW7 and low MAP4 was an independent prognostic indicator and prospective longer survival. Moreover, a combination regimen that included MK-8353 to inhibit the phosphorylation of ERK and bevacizumab to inhibit VEGFA produced potent inhibitory effects on the growth of FBXW7 inactivation xenograft tumors in vivo. CONCLUSIONS: This study provided evidence that FBXW7 loss of function promoted ESCC via MAP4 overexpression and ERK phosphorylation, and this novel FBXW7/MAP4/ERK axis may be an efficient target for ESCC treatment.

A circular RNA hsa_circ_0079929 inhibits tumor growth in hepatocellular carcinoma.

PURPOSE: Most recently, circular RNAs (circRNAs) were considered playing regulatory roles in tumor initiation and development. The specific function of circRNAs in hepatocellular carcinoma (HCC) remains unknown. This study was designed to detect specific roles of a circRNA hsa_circ_0079299 in HCC. METHODS: The expression of hsa_circ_0079299 in HCC and tumor cell lines was detected using quantitative PCR (qPCR). Cell proliferation, migration, cell cycle and apoptosis after overexpression of the circRNA were measured using cell counting kit-8 (CCK8) assay, colony formation, 5-ethynyl-2'-deoxyuridine (EdU) assay, wound healing assay, transwell culture system and flow cytometry. Western blotting assay detected the protein expression of PI3K/AKT/mTOR signaling pathway and cyclin B1 (CCNB1). Overexpression of the circRNA in vivo was measured by nude mice tumorigenesis. RESULTS: The expression of hsa_circ_0079299 was lower in HCC tissues. Overexpression of hsa_circ_0079299 suppressed tumor growth in vitro and in vivo, retarded cell cycle progression while had no effect on cell migration and apoptosis. The inhibitory effect of hsa_circ_0079299 was partly mediated by PI3K/AKT/mTOR signaling pathway. CONCLUSION: Our study shows that tumor suppressive role of hsa_circ_0079299 in HCC provides new recognition of circRNAs in cancers.

The effect and mechanism of miR-210 in down-regulating the autophagy of lung cancer cells.

This project aims to investigate the roles of miR-210 in autophagy of lung cancer cells and the related mechanism. The expressions of miR-210 and ATG7 in 30 cancer tissues and the adjacent tissues in patients with lung cancer were compared using RT-qPCR methods, Western Blot assay was carried out to test the expression of ATG7 in protein. Moreover, the dual luciferase reporter gene assay system was used to confirm ATG7 is a target gene of miR-210. Furthermore, lung cancer cell line A549 was transfected with either miR-210 mimics or inhibitors and RT-qPCR methods was used to detect the expression of miR-210 and ATG7. Next, MTT assay was used to examine the effect of miR-210 on the growth of the lung cancer cells, and finally, the expression of autophagy related genes, ATG7, LC3-II/LC3-I and Beclin-1 were detected by Western Blot and ICC assay. We observed that miR-210 was significantly increased and ATG7 was markedly decreased in cancer tissue of patients with lung cancer compared with normal tissue. Moreover, results of dual luciferase reporter assay indicated that ATG7 is a direct target of miR-210. Next, transfection of miR-210 mimics in lung cancer cells induced significant increase in cell proliferation, and transfection of miR-210 inhibitors lead to inhibited cell proliferation. Furthermore, over-expression of miR-210 induced marked decrease in the expression of ATG7, LC3-II/LC3-I and Beclin-1, while transfection of miR-210 inhibitors induced significant increase in the expression of ATG7, LC3-II/LC3-I and beclin-1. Our results suggested that miR-210 plays a great role in autophagy of lung cancer cell by targeting ATG7.

Circulating tumor cell levels and carcinoembryonic antigen: An improved diagnostic method for lung adenocarcinoma.

BACKGROUND: The aim of this study was to determine a correlation between benign and malignant lung solitary pulmonary nodules (SPN), and analyze the association between circulating tumor cell (CTC) levels and different subtypes of lung adenocarcinoma. METHODS: A total of 200 patients (80 with SPNs and 120 diagnosed with lung cancer) were included in the study. The CTC levels were quantified by identifying the folate receptor on the surface of tumor cells; clinical tumor specific markers were detected by biochemical immunization. The content of peripheral blood CTCs in benign and malignant lung SPN patients was detected and the differences in preoperative CTC levels in different pathological subtypes were analyzed. Based on the collected data, receiver operating characteristic curves were calculated and the rate of lung cancer was predicted. RESULTS: The peripheral blood CTC levels in patients with malignant lung SPNs were higher than in patients with benign SPNs. The maximum nodule diameter, carcinoembryonic antigen, and CTC levels were independent risk factors for malignant lung SPNs. The peripheral blood CTC levels in patients with stage III-IV lung adenocarcinoma were higher than in stage I-II patients. The peripheral blood CTC levels in patients with microinvasive and invasive adenocarcinoma were higher than in adenocarcinoma in situ patients. The CTC levels in the peripheral blood of patients with maximum tumor diameter > 2 cm were higher than in patients with tumors < 2 cm. CONCLUSION: The detection of CTCs can be used as a biomarker for screening SPNs and diagnosing early-stage lung cancer. Using the combination of CTC levels and CEA significantly improves the efficacy of lung adenocarcinoma diagnosis.