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Background: Non-small cell lung cancer (NSCLC) is the most common malignancy and one of the most common causes of cancer-related death worldwide. Robotic-assisted thoracic surgery (RATS) has gradually become a prevalent surgical method for patients with NSCLC. Previous studies have found that body mass index (BMI) is associated with postoperative outcomes. This study aimed to investigate the effectiveness of RATS compared to video-assisted thoracic surgery (VATS) in the treatment of NSCLC with different BMI, in terms of perioperative outcomes. Methods: The baseline and perioperative data, including BMI, of 849 NSCLC patients who underwent minimally invasive anatomic lung resections from August 2020 to April 2021 were retrospectively collected and analyzed. Propensity score matching analysis was applied to minimize potential bias between the two groups (VATS and RATS), and the perioperative outcomes were compared. Subgroup analysis was subsequently performed. Results: Compared to VATS, RATS had more lymph nodes dissected {9 [inter-quartile range (IQR), 6-12] vs. 7 (IQR, 6-10), P

As a part of R&D work for the high intensity proton linac of China Accelerator Driven Sub-critical System project, a superconducting half-wave cavity with a frequency of 162.5 MHz and an optimal beta of 0.15 (HWR015) has been developed at Institute of Modern Physics (IMP), Chinese Academy of Sciences. In this paper, the design and test results will be described in detail. We introduced a new stiffening strategy for the HWR cavity, the simulation results show that the cavity has much lower frequency sensitivity coefficient (df/dp), Lorentz force detuning coefficient (KL), and can achieve more stable mechanical properties. The performance of the HWR cavity operated in cryostat will be also reported.

BACKGROUND: Lung cancer is one of the most common causes of cancer-related death worldwide. The enhanced recovery after surgery (ERAS) program is an effective evidence-based multidisciplinary protocol of perioperative care. However, the roles of ERAS in lung cancer surgery remain unclear. This systematic review and meta-analysis aimed to investigate the short-term impact of the ERAS program on lung resection surgery, especially in relation to postoperative complications. METHODS: A systematic literature search of PubMed, EMBASE, and the Cochrane Library databases until October 2020 was performed to identify the studies that implemented an ERAS program in lung cancer surgery. The studies were selected and subjected to data extraction by 2 reviewers independently, which was followed by quality assessment. A random effects model was used to calculate overall effect sizes. Risk ratio (RR), risk difference (RD), and standardized mean difference (SMD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. Subgroup analysis and sensitivity analysis were subsequently performed. RESULTS: A total of 21 studies with 6,480 patients were included. The meta-analysis indicated that patients in the ERAS group had a significantly reduced risk of postoperative complications (RR =0.64; 95% CI: 0.52 to 0.78) and shortened postoperative length of stay (SMD=−1.58; 95% CI: −2.38 to −0.79) with a significant heterogeneity. Subgroup analysis showed that the risks of pulmonary (RR =0.58; 95% CI: 0.45 to 0.75), cardiovascular (RR =0.73; 95% CI: 0.59 to 0.89), urinary (RR =0.53; 95% CI: 0.32 to 0.88), and surgical complications (RR =0.64; 95% CI: 0.42 to 0.97) were significantly lower in the ERAS group. No significant reduction was found in the in-hospital mortality (RD =0.00; 95% CI: −0.01 to 0.00) and readmission rate (RR =1.00; 95% CI: 0.76 to 1.32). In the qualitative review, most of the evidence reported significantly decreased hospitalization costs in the ERAS group. CONCLUSIONS: The implementation of an ERAS program for surgery of lung cancer can effectively reduce risks of postoperative complications, length of stay, and costs of patients who have undergone lung cancer surgery without compromising their safety.

The in-situ plasma cleaning technique using the chemical reactive oxygen plasma to remove the hydrocarbon contaminants , the outmost layer of the inner surface of the HWR cavity, has been explored at Institute of Modern Physics, CAS. For the purpose of cleaning the HWR cavity in the cryomodule by plasma, an offline apparatus for the plasma discharge study was set up, which duplicates the assembly of the cavity inside the cryomodule. Plasma ignition procedures were investigated. And the plasma parameters such as free electron number density, electron temperature and dissociated oxygen atom intensity were diagnosed by optical emission spectra to optimize the operation conditions for plasma in-situ cleaning of the HWR cavity. To evaluate the efficiency of the plasma in-situ cleaning of the HWR cavity, the related experiments were carried out on the vertical test stand. The results show that the hydrocarbon contaminants on the inner surface of the cavity were removed, and the maximal available accelerating gradient of the cavity was improved by 29% due to the mitigation of field emission inside the cavity after plasma cleaning. Details of these experimental results and observations are discussed in this article.

The resection of nodules by thoracoscopic surgery is difficult because the nodules may be hard to identify. Preoperative localization of pulmonary nodules is widely used in the clinic. In this study, we retrospectively compared CT-guided hook wire localization and electromagnetic navigation bronchoscopy (ENB) localization of small pulmonary nodules before resection. Patients who underwent localization with CT-guided hook wire or ENB followed by video-assisted thoracoscopic surgery (VATS) at Qilu Hospital of Shandong University between January 2016 and December 2019 were retrospectively included. Clinical parameters, complication and failure rate, and localization time were compared between two groups. A total of 157 patients underwent the localization procedure successfully. Pulmonary nodules were localized by CT-guided hook wire in 105 patients and by ENB in 52 patients. The nodule size in ENB group was smaller than that in CT-guided localization group (P P = 0.0058). In CT-guided localization group, 6 patients failed to be located while none failed in ENB group (P = 0.079). The procedure time was 15.15 ± 3.70 min for CT-guided localization and 21.29 ± 4.00 min for ENB localization (P

Background: Many evidences proved important roles of microRNAs in the occurrence and development of non-small cell lung cancer (NSCLC). This work aimed to explore the effects and regulating mechanism of microRNA-665 (miR-665) in NSCLC. Methods: Here, quantitative real time PCR was used to evaluate the expression level of miR-665 in NSCLC tissues and several cell lines (H520, H1299, PC9, H358, and A549). Then, MTT, apoptosis assays and wound-healing assays were performed to study miR-665 functions on cell proliferation, apoptosis and migration. Based on bioinformatics analysis, nemo-like kinase (NLK) was predicted as a potential target of miR-665 and then a series of experiments were performed to explore miR-665 mechanism.Results: In NSCLC tissues and several cell lines, miR-665 was up-regulated and cell experiments displayed that it had abilities to promote cell proliferation and migration, and inhibit cell apoptosis. MiR-665 over-expression could reduce NLK mRNA and protein level by binding to 3′-untranslated region of NLK, which suggested that miR-665 could regulate NLK expression. Further analysis found that there was an inverse correlation f between miR-665 and NLK in NSCLC. Moreover, low-level NLK possessed same effects on cells as miR-665 over-expression, and its knockdown could partly recovery the miR-665-mediated cell proliferation, migration and anti-apoptosis, indicating that miR-665 might regulate biological behaviors of NSCLC cells via targeting NLK. Conclusion: MiR-665 probably promoted NSCLC occurrence and progression via targeting NLK, which might be a hopeful biomarker for NSCLC diagnosis or a target for treatment.

Objective. This Work is aimed at exploring the effect of microRNA (MiR)-608 on the function of nonsmall cell lung cancer (NSCLC) A549 cells and related mechanisms. Methods. Blood samples of 106 NSCLC patients (experimental group) as well as 124 normal people (control group) were selected for relevant investigation. Polymerase chain reaction (PCR) as well as DNA sequencing was used to determine the genotyping of the MiR-608 rs4919510 polymorphism. MiR-608 expression in cells was detected by real-time PCR technology. Western blotting was used to detect changes in protein levels. NSCLC tissues as well as adjacent tissues were explored in 33 patients undergoing surgery. Results. MiR-608 rs4919510 does not influence the incidence of NSCLC patients. In addition, MiR-608 expression was downregulated in the tumor tissue of NSCLC patients, while the transcription factor activating enhancer-binding protein 4 (TFAP4) expression was upregulated. MiR-608 promotes DOX- (Doxorubicin-) induced apoptosis by negatively regulating TFAP4 expression in NSCLC tissue. TFAP4 can significantly inhibit the migration of A549 cells. Conclusion. The findings in this investigation can contribute to the effective treatment of NSCLC patients. Also, the investigation can provide some theoretical support for the application of new targets for NSCLC treatment.

OBJECTIVE To investigate the effect of ZHX2 on lung cancer cells proliferation and apoptosis. MATERIALS AND METHODS The mRNA and protein expression of ZHX2 were detected by qRT-PCR and western blot, respectively. The human lung cancer cells were divided into Control, NC, ZHX2, SB, and ZHX2 + Ani groups. The cell proliferation was detected by CCK-8 assay and the cell migration and invasion were detected by Transwell assay. Cell apoptosis was detected by flow cytometry. Apoptosis and p38MAPK signaling pathway related proteins were detected by western blot. The nude mice model of lung cancer xenograft was constructed. The tumor volume and tumor weight were measured. The expression of PCNA protein in tumor tissues was detected by immunohistochemistry. The apoptosis of tumor cells was detected by TUNEL staining. The ZHX2 and p38MAPK signaling pathway related proteins in tumor tissues were detected by western blot. RESULTS The expression of ZHX2 gene and protein in the cancer cell lines were significantly decreased. Compared with control and NC groups, the cells proliferation, migration and invasion were inhibited in ZHX2 and SB groups, while the apoptosis and apoptosis related proteins were increased (p< 0.05). Meanwhile, compared with ZHX2 group, the tumor growth rate, volume, weight, the percentage of PCNA-positive cells, and p-P38 MAPK/P38 MAPK were increased significantly in ZHX2 + Ani group, while the apoptotic index and the expression of MMP-9 protein were significantly decreased (p< 0.05). CONCLUSION ZHX2 could inhibit proliferation and promote apoptosis of lung cancer cells by inhibiting p38MAPK signaling pathway.

Background: The resection of nodules by thoracoscopic surgery is difficult because the nodules may be hard to identify. Currently, preoperative localization of pulmonary nodules is widely used in the clinic, including Computed Tomographic Imaging (CT)-guided transthoracic approach, hook-wire and coil embolization, but these methods increase radiation exposure and cause complications. Methods: In this study, we retrospectively compared electromagnetic navigation bronchoscopy (ENB) guided and CT guided localization of small pulmonary nodules before resection. Results: Total 157 patients underwent the localization procedure successfully, and the nodules were localized by CT guidance in 105 patients and by ENB in 52 patients. The nodule size of magnetic navigation localization was smaller than that of CT-guided localization (P

MicroRNAs (miRNAs/miRs) are a class of small, highly conserved non-coding RNAs that can serve either oncogenic or tumor-suppressive roles in a wide variety of tumors. miR-200c is a member of the miR-200 family whose specific role in non-small cell lung cancer (NSCLC) has not yet been elucidated. The purpose of the present study was to detect the expression level of miR-200c in NSCLC, and to analyze its association with clinicopathological factors and patient prognosis. The present study determined the expression levels of miR-200c in 110 tumor samples collected from patients diagnosed with NSCLC who underwent complete tumor resection with regional lymph node dissection, as assessed by reverse transcription-quantitative polymerase chain reaction. The association between the expression level of miR-200c and clinicopathological features and patient prognosis was also analyzed. The results showed that miR-200c overexpression was detected in 66 of the 110 cases and was significantly associated with positive lymph node metastasis (P

Background Circular RNA (circRNA) has become a new focus in the field of tumor biology research in recent years. Many circRNAs have been showed to play an important role in the progression of lung adenocarcinoma (LUAD). In this work, we studied the oncological role of hsa-circ-000881 in LUAD and attempted to explore the related mechanism. Methods The relative expressions of hsa-circ-000881, miR-665, and PRICKLE2 were detected by RT-qPCR or western blot. Functional assays were conducted to analyze the role of hsa-circ-000881 in the proliferation, migration, and invasion of LUAD cells. A luciferase reporter assay was performed to verify whether hsa-circ-000881, miR-665, and PRICKLE2 interact with each other. Results Circ-000881 was remarkably downregulated in LUAD. Overexpression of circ-000881 attenuated cell growth, migration, and invasion, whereas its knockdown enhanced the malignancy of LUAD cells. The results of luciferase reporter assay and bioinformatics analysis confirmed that circ-000881 served as a sponge for miR-665, and PRICKLE2 was a direct target of miR-665.Overexpression of miR-665 or silencing of PRICKLE2 abolished circ-000881-mediated inhibition of malignant tumor behavior in LUAD cells. Conclusions Circ-000881 has inhibitory effects on LUAD via a miR-665/PRICKLE2 axis, suggesting that circ-000881 may be an underlying therapeutic target for LUAD.

650 MHz multicell superconducting radio frequency (SRF) elliptical cavities are proposed for effective acceleration of proton beam in the Chinese initiative Accelerator Driven Subcritical System (CiADS). Two families of such cavities will be used in the driver superconducting linac to accelerate the H + beam from 175 MeV to 500 MeV, with the possibility to upgrade the energy to 1 GeV and higher. Detail designs of a six-cell β o p t = 0.62 elliptical cavity and a five-cell β o p t = 0.82 elliptical cavity will be presented in this paper, including the multi-parameter electromagnetic design and optimization, high order modes analyses, multipacting simulations, mechanical and engineering analyses. Sub-systems of the cavity such as the fundamental power coupler antenna tip design and mechanical design of cavity-helium vessel-tuner system will also be discussed in detail. Three single cell prototype cavities were fabricated and vertical tested to verify the electromagnetic properties, the fabrication and post-processing technologies. Four multi-cell prototype cavities are under manufacturing and expected to be ready in 2021.

The conventional video-assisted thoracoscopic surgery (VATS) is performed through the intercostals incisions. In this study, we reported our current experience of thoracoscopic surgery using a subxiphoid single-incision and compared it with the intercostal uniport VATS in the operation time and postoperative pain for spontaneous pneumothorax.From July 2014 to September 2015, 43 consecutive patients with spontaneous pneumothorax underwent the unilateral or bilateral bullectomy vie VATS. Among these, 22 patients were treated by the subxiphoid single-incision VATS, and 21 patients were treated using the conventional intercostals uniport VATS. The duration of operation, hospital stay days and inpatient pain scores were compared between each group.The postoperative pain scores on postoperative days (POD) 0, 1, 2 and 3 were significantly lower for patients who underwent the subxiphoid single-incision VATS than those who underwent the intercostal uniport VATS (p 0.05). However, the subxiphoid single-incision VATS needed longer surgical time than the intercostal uniport VATS (p 0.001).The subxiphoid uniport VATS could decrease the postoperative pain and was safe and effective for performing the unilateral or bilateral bullectomy, but, demanded longer surgical time comparing with the intercostal uniport VATS.Subxiphoid single-incision VATS, as a new method for bullectomy, could provide a good choice of the incision position for these young patients with spontaneous pneumothorax.

Reactive oxygen species (ROS) are at the center of many physiological and pathological processes. ROS generated due to oxidative stress can potentiate both cancer initiation and progression. Rotenone, which is an inhibitor of the mitochondrial electron transport chain complex I, results in the activation of NOX2 and release of ROS, and has been shown to display anticancer activity through the induction of apoptosis in various cancer cells. The mechanistic link between rotenone-dependent activation of NOX2 and induction of apoptosis is still elusive. In this study, we used the human lung cancer A549 cells to study the molecular mechanism(s) involved between rotenone-dependent activation of NOX2 and impairment of autophagic machinery. We report that acute exposure to rotenone induced mild NOX2-dependnet oxidative stress, which impaired the autophagic flux, resulting in cytosolic accumulation of LC3 and p62/STSQM1. We further show that this induction occurs through the PI3K/Akt/mTORC1 signaling pathway. We furthermore show that chronic exposure to rotenone lead to excessive NOX2-dependent ROS generation, increases autophagy, and decreases p62 level via increased-autophagic flux. Taken together, this study is the first mechanistic elucidation of how rotenone can be used to potently target cancer cells without overhauling the entire cellular machinery. © 2016 IUBMB Life 68(5):388-393, 2016.

A 162.5 MHz superconducting half-wave cavity with an optimizing beta of 0.10 (HWR010) has been developed for China Accelerator Driven Sub-Critical System (CADS) Project at Institute of Modern Physics (IMP), Chinese Academy of Sciences. In this paper, the detailed development of the HWR010 cavity will be presented, and will mainly focus on the mechanical design and the corresponding test results. A new stiffening strategy is proposed for the cavity. Compared to the original scheme of the stiffening design for the cavity, the simulation results of the frequency shift for the cavity adopted the new stiffening strategy show that the cavity has much lower frequency sensitivity coefficient (df/dp) and Lorentz force detuning coefficient (KL), and good mechanical stability.

Mechanical vibrations of the superconducting cavity, also known as microphonics, cause shifts in the resonant frequency of the cavity. In addition to requiring additional RF power, these frequency shifts can contribute to errors in the closed loop phase and amplitude regulation. In order to better understand these effects, a new microphonics measurement method was developed, and the method was successfully used to measure microphonics on the half-wave superconducting cavity when it was operated in a production style cryostat. The test cryostat held a single β ¼0.1 half-wave cavity which was operated at 162.5 MHz Yue et al. (2013) and Wang et al. (2013) [1,2]. It is the first time that the National Instruments PXIe-5641R intermediate frequency transceiver has been used for microphonics measurements in superconducting cavities. The new microphonics measurement method and results will be shown and analyzed in this paper.

Transient beam loading effect is one of the key issues in any superconducting accelerators, which needs to be carefully investigated. The core problem in the analysis is to obtain the time evolution of cavity voltage under the transient beam loading. To simplify the problem, the second order ordinary differential equation describing the behavior of the cavity voltage is intuitively simplified to a first order one, with the aid of the two critical approximations lacking the proof for their validity. In this paper, the validity is examined mathematically in some specific cases, resulting in a criterion for the simplification. It's popular to solve the approximated equation for the cavity voltage numerically, while this paper shows that it can also be solved analytically under the step function approximation for the driven term. With the analytical solution to the cavity voltage, the transient reflected power from the cavity and the energy gain of the central particle in the bunch can also be calculated analytically. The validity of the step function approximation for the driven term is examined by direct evaluations. After that, the analytical results are compared with the numerical ones., To be published in Chinese Physics C

Lysosome-associated protein transmembrane-4β (LAPTM4B) is a novel cancer-related gene that is upregulated in many tumors, and which plays important roles in carcinogenesis. It has two alleles, LAPTM4B 1 and LAPTM4B 2. LAPTM4B 1 contains only one copy of a 19-bp sequence in the first exon, whereas LAPTM4B 2 contains two tight tandem segments. Previous studies have shown that LAPTM4B 2 is a risk factor for susceptibility and prognosis of many tumors. The present study investigated the relationship between LAPTM4B polymorphism and non-small cell lung cancer (NSCLC) susceptibility and prognosis. We identified LAPTM4B genotypes with polymerase chain reaction (PCR) in peripheral blood samples. In the adjusted multivariate logistic regression analysis, we found that LAPTM4B 1/2, LAPTM4B 2/2 exhibited 1.48-fold [95% confidence interval (CI), 1.076-2.037] and 2.855-fold (95%CI, 1.722-4.734) increases in the risk of developing NSCLC compared with non-LAPTM4B 2 carriers. Furthermore, our results showed that overall survival time and disease-free survival time of patients with LAPTM4B 2 were significantly shorter than in patients carrying LAPTM4B 1 (P=0.001 and P=0.001, respectively). In addition, multivariate Cox regression analysis revealed that LAPTM4B 2 was also an independent prognostic factor for NSCLC. These results suggest that LAPTM4B polymorphisms may be a prospective marker for evaluating the risk and prognosis of NSCLC.

Heparanase is a mammalian endoglycosidase that degrades heparan sulfate at the cell surface and in the extracellular matrix. The expression of heparanase was detected in a wide variety of human malignant tumors and closely associated with tumor invasion, metastasis, and angiogenesis. However, the specific roles of heparanase and its mechanisms of regulating the malignant potential of non-small cell lung cancer (NSCLC) cells still remain unclear. In the present study, the expression of heparanase was down-regulated in NSCLC cell line by antisense oligodeoxynucleotide. Results showed that down-regulation of heparanase led to significant inhibition of invasive and proliferative potentials of A549 cells in vitro and in vivo. Further research demonstrated that down-regulation of heparanase significantly inhibited the angiogenic potential of A549 cells, which might be the mechanism responsible for the inhibition of A549 cell proliferation in BALB/c nude mice in vivo. These findings demonstrate that heparanase plays essential roles in regulating the invasion, proliferation, and angiogenesis of A549 cells.

Neuregulin-1 (NRG-1) signaling regulates neuronal development, migration, myelination, and synaptic maintenance. Three members of tyrosine kinase receptor (Trk) family, TrkA, TrkB, and TrkC, have been identified in DRG neurons. Whether NRG-1β and its signaling pathways influence the expression of these Trk receptors in DRG neurons is still unclear. In the present study, primary cultured DRG neurons were used to determine the effects of NRG-1β on TrkA, TrkB, and TrkC expression in DRG neurons with excitotoxicity induced by glutamate (Glu). The involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and the effects of extracellular signal-regulated protein kinase (ERK1/2) signaling pathways on NRG-1β were also determined. DRG neurons were cultured for 48h and then exposed to Glu, Glu plus NRG-1β, LY294002 plus Glu plus NRG-1β, PD98059 plus Glu plus NRG-1β, and PD98059 plus LY294002 plus Glu plus NRG-1β for an additional 24h. The DRG neurons were continuously exposed to culture media as a control. After that, all cultures were processed for detection of mRNA levels of TrkA, TrkB, and TrkC using real time-PCR analysis. Protein levels of TrkA, TrkB, and TrkC were detected using a Western blot assay. The expression of TrkA, TrkB, and TrkC in situ was determined by a fluorescent labeling technique. The levels of phosphorylated Akt (pAkt), phosphorylated ERK1/2 (pERK1/2), total protein levels of Akt and ERK1/2 were detected using a Western blot assay. The results indicated that in primary cultured DRG neurons with excitotoxicity induced by Glu, NRG-1β increased the expression of TrkA and TrkB their mRNAs, but not TrkC and its mRNA. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1β. NRG-1β may play an important role in regulating the expression of different Trk receptors in DRG neurons through the PI3K/Akt and ERK1/2 signaling pathways.

A 325-MHz superconducting half-wave resonator has been designed with β = 0.51. Three shapes of the inner conductors (race track, ring shape and elliptical shape) were optimized to decrease the peak electromagnetic fields and minimize the dissipated RF power on the cavity walls. In order to suppress the operation frequency shift caused by fluctuations of the helium pressure and maximize the tuning ranges, the frequency shifts and mechanical properties were studied on the electric and magnetic areas. The helium vessel was designed to keep the mechanical structure as robust as possible.

Lung cancer is the leading cause of cancer-related mortality all over the world. In recent years, pulmonary adenocarcinoma has surpassed squamous cell carcinoma in frequency and is the predominant form of lung cancer in many countries. Epidemiological investigations have shown an inverse relationship between garlic (Allium sativum) consumption and death rate from many cancers. Diallyl trisulfide (DATS) is one of the garlic-derived compounds (also known as: organosulfer compounds, OSC). DATS can induce apoptosis and inhibit the growth of many cancer cell lines. Our study demonstrated that the apoptotic incidents induced by DATS were a mitochondria-dependent caspase cascade through a significant decrease of the anti-apoptotic Bcl-2 that resulted in up-regulation of the ratio of Bax/Bcl-2 and the activity of caspase-3, -8, and -9. Eventually, DATS induced the apoptosis and inhibited the proliferation in a concentration- and time-dependent manner. Furthermore, by establishing an animal model of female BALB/c nude mice with A549 xenografts, we found that oral gavage of DATS significantly retarded growth of A549 xenografts in nude mice without causing weight loss or any other side effects compared with the control group. All the evidence both in vitro and in vivo suggested that DATS could be an ideal anti-cancer drug.

The high-current superconducting proton linac is being studied for the accelerator-driven system (ADS) project undertaken by the Chinese Academy of Sciences. The injector II will be operated at 162.5 MHz, and the proton out from the RFQ with an energy of 2.5 MeV will be accelerated to 10 MeV by two cryo-modules, which are composed of eight superconducting half wave resonance cavities and nine solenoids. In this paper, the design and beam simulation of the superconducting section of the injector II, the acceptance calculation and a stability analysis are presented.

The purposes of the present study were to detect the expression of metastasis-associated protein 1 (MTA1) in patients with esophageal squamous cell cancer (ESCC), and to evaluate the relevance of MTA1 protein expression to the tumor progression, angiogenesis, and prognosis. Both MTA1 protein and intratumoral microvessels were examined by immunohistochemical staining in 131 ESCC patients who successfully underwent subtotal esophagectomy and esophagogastric anastomosis at Qilu Hospital between Jan 2004 and Dec 2005. Intratumoral microvessel density (MVD) was recorded by counting CD-34 positive immunostained endothelial cells. All statistical analyses were performed with SPSS 13.0 statistical software. High expression of MTA1 protein was detected in 57 cases and significantly correlated with tumor invasion depth (P = 0.041), lymph node metastasis (P = 0.021), pathologic stage (P = 0.003), and MVD (P = 0.044). Survival analysis showed that patients with MTA1 protein high expression had significantly poor overall 5-year survival (P = 0.002), and the factor found on multivariate analysis to significantly affect overall survival was only pathologic stage (P = 0.040). Further stratified survival analysis split by pathologic stage demonstrated that MTA1 protein high expression significantly predicted unfavorable prognosis among patients with pathologic stage II disease (P = 0.006). High expression of the MTA1 protein is common in ESCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. These findings indicate that MTA1 protein has clinical potentials as a useful indicator of progressive phenotype, a promising prognostic predictor to identify patients with poor prognosis, and a potential novel therapeutic target of antiangiogenesis for patients with ESCC.

Reactive oxygen species (ROS) are at the center of many physiological and pathological processes. ROS generated due to oxidative stress can potentiate both cancer initiation and progression. Rotenone, which is an inhibitor of the mitochondrial electron transport chain complex I, results in the activation of NOX2 and release of ROS, and has been shown to display anticancer activity through the induction of apoptosis in various cancer cells. The mechanistic link between rotenone-dependent activation of NOX2 and induction of apoptosis is still elusive. In this study, we used the human lung cancer A549 cells to study the molecular mechanism(s) involved between rotenone-dependent activation of NOX2 and impairment of autophagic machinery. We report that acute exposure to rotenone induced mild NOX2-dependnet oxidative stress, which impaired the autophagic flux, resulting in cytosolic accumulation of LC3 and p62/STSQM1. We further show that this induction occurs through the PI3K/Akt/mTORC1 signaling pathway. We furthermore show that chronic exposure to rotenone lead to excessive NOX2-dependent ROS generation, increases autophagy, and decreases p62 level via increased-autophagic flux. Taken together, this study is the first mechanistic elucidation of how rotenone can be used to potently target cancer cells without overhauling the entire cellular machinery. © 2016 IUBMB Life 68(5):388-393, 2016.

A new procedure for the design and simulation of a Radio Frequency Quadrupole (RFQ) accelerator has been developed at the Argonne National Laboratory. This procedure is integrated with the beam dynamics design code DESRFQ and the simulation code TRACK, which are based on three-dimensional field calculations and the particle-in-cell mode beam dynamics simulations. This procedure has been applied to the development of a 162.5 MHz CW RFQ which is capable of delivering a 10 mA proton beam for the Accelerator Driven System (ADS) of the CAS. The simulation results show that this RFQ structure is characterized by the stable values of the beam acceleration efficiency for both the zero current beam and space charge dominated beam. For an average beam current of 10 mA, there is no transverse rms emittance growth, the longitudinal rms emittance at the exit of RFQ is low enough and there is no halo formation. The beam accelerated in the RFQ could be accepted easily and smoothly by the following super-conducting linear accelerator.

The ABC code is an optimization program for the development of matching channels and dynamical matchers in radio frequency quadrupole (RFQ) structures, and a new approach to this code to define the geometry of the radial matching section of the RFQ has been developed. This approach is based on the application of the numerical optimization step by step. This optimization is intended to search for the initial matching condition of a beam, the optimization of parameters of a cell of the channel on given characteristic parameters and traces of a beam in linear channels in both forward and backward directions. To further verify the results of the optimization, multi-particle beam dynamics simulations have been carried out using the BEAMPATH and TRACK codes. The result of the beam dynamics simulation shows that the optimization result of the ABC code is reasonable and this approach provides an opportunity to redesign the structure of the radial matching section of the RFQ.

Nowadays, some evidences demonstrate that human mesenchymal stem cells (hMSCs) favor tumor growth; however, others show that hMSCs can suppress tumorigenesis and tumor growth. With the indeterminateness of the effect of hMSCs on tumors, we investigated the effect of hMSCs on lung cancer cell line A549 and esophageal cancer cell line Eca-109 in vitro and in vivo. Our results revealed that hMSCs inhibited the proliferation and invasion of A549 and Eca-109 cells, arrested tumor cells in the G1 phase of the cell cycle and induced the apoptosis of tumor cells in vitro by using a co-culture system and the hMSCs-conditioned medium. However, animal study showed that hMSCs enhanced tumor formation and growth in vivo. Western blotting and immunoprecipitation data showed that the expressions of proliferating cell nuclear antigen (PCNA), Cyclin E, phospho-retinoblastoma protein (pRb), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL, and matrix metalloproteinase 2 (MMP-2) were downregulated and the formation of Cyclin E-cyclin-dependent kinase 2 (CDK2) complexes was inhibited in the tumor cells treated with the hMSCs-conditioned medium. According to the observation of tumor mass and the result of microvessel density (MVD), we found that the promoting role of hMSCs on tumor growth was related with the increase of tumor vessel formation. Our present study suggests that hMSCs have a contradictory effect on tumor cell growth between in vitro and in vivo, and therefore, the exploitation of hMSCs in new therapeutic strategies should be cautious under the malignant conditions. J. Cell. Physiol. 226: 1860–1867, 2011. © 2010 Wiley-Liss, Inc.

Human mesenchymal stem cells (hMSCs) are mostly studied for their potential clinical use. Recently, much attention in the field of cancer research has been paid to hMSCs. In this study, we investigated the influence of hMSCs on the proliferation of lung cancer cell lines SK-MES-1 and A549 in vitro and in vivo by using a co-culture system and the hMSCs-conditioned medium. Our results demonstrated that hMSCs could inhibit the proliferation of SK-MES-1 and A549 cells, and induce the apoptosis of tumor cells in vitro via some soluble factors. Animal study showed that these soluble factors from hMSCs could suppress tumorigenesis and tumor angiogenesis by treating preliminarily tumor cells with the hMSCs-conditioned medium. The downregulated expression of vascular endothelial growth factor in tumor cells might be the mechanism of interference in tumor angiogenesis, which was verified by western blot analysis and immunohistochemistry assay. Taken together, our results suggested that the hMSCs could inhibit tumor cell growth by secreting some soluble factors.

Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma.

The nuclear receptor coactivator 5 (NCOA5) was a unique coactivator independent of AF2 that can modulate ERα-mediated transcription. Recent researches have indicated that its downregulation may participate in cancer development and progression. The aims of the present study were to investigate NCOA5 expression in esophageal squamous cell carcinoma (ESCC) and validate its possible influence on patients' prognosis. NCOA5 expression was examined by immunohistochemical staining in 119 ESCC patients' tissues. Ten paired tumor and adjacent normal specimens were examined by Western blot analysis. Statistical analysis was performed to assess its relevance with various clinicopathologic features and its influence on patients' survival. By immunohistochemistry analysis, NCOA5 expression was found to be significantly correlated with differentiation (P = 0.039), T status (P = 0.047) and stage (P = 0.036). Furthermore, we found NCOA5 higher expression in normal tissues than in tumor tissues by Western blot analysis. Univariate analysis showed that poor differentiation (P = 0.035, P = 0.027), lymph node metastasis (P < 0.001, P < 0.001), high T status (P = 0.010, P = 0.012), advanced stage (P < 0.001, P < 0.001) and NCOA5 low expression (P < 0.001, P < 0.001) were significantly correlated with poor prognosis of both disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that NCOA5 low expression (P = 0.019, P = 0.047), high T status (P = 0.015, P = 0.012), lymph node metastasis (P = 0.040, P = 0.021) and advanced stage (P = 0.017, P = 0.046) were independent prognostic factors of poor DFS and OS. Our findings suggest that NCOA5 low expression is associated with ESCC progression and is a potential biomarker in predicting poor prognosis. Further studies of NCOA5 may help develop new therapeutic strategies against ESCC.

Background: Golgi phosphoprotein-3 (GOLPH3) is implicated in cancer development and progression. The aim of this study was to evaluate the prognostic significance of GOLPH3 protein and its association with tumor angiogenesis in patients with early-stage NSCLC. Materials and Methods: Immunohistochemistry was performed to determine GOLPH3 protein expression and allow assessment of intratumoral microvessel density (MVD) by counting CD-34 positive immunostained endothelial cells. Correlations of expression with MVD, clinicopathologic features and clinical prognosis were analyzed. Results: A notably higher level of GOLPH3 expression was found in early-stage NSCC tissues at the protein level. However, we do not find any correlation between GOLPH3 expression and clinicopathologic features (p>0.05), although higher MVD was positively associated with GOLPH3 overexpression (p

Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel oncogene, which has been indicated to be dramatically overexpressed in various malignant tumors. The aims of this study were to detect LAPTM4B protein expression in patients with non-small cell lung cancer (NSCLC) and then analyze the relationships of LAPTM4B protein with clinicopathologic factors, tumor angiogenesis and prognosis with SPSS statistical software. Immunohistochemistry was used to examine the expression of LAPTM4B and CD34 proteins in NSCLC tissues, and its results showed that LAPTM4B protein expression in NSCLC tissues was significantly higher than that in normal lung tissues (P < 0.001). Of the186 NSCLC cases, 129 (69.35 %) had strong expression of LAPTM4B protein, which was associated with histopathologic differentiation (P = 0.017), lymph node metastasis (P = 0.001) and TNM stage (P = 0.046), as well as the microvessel density (MVD) (P = 0.019). Kaplan-Meier survival analysis revealed that patients with strong LAPM4B protein expression and high MVD might have poor overall survival (OS; P = 0.001, P = 0.002, respectively) and disease-free survival (DFS; P = 0.002, P = 0.038, respectively). Multivariate analysis demonstrated that LAPTM4B protein was an independent prognostic marker for OS and DFS of NSCLC patients (P = 0.037, P = 0.046, respectively). These findings illustrated that LAPTM4B protein was closely associated with NSCLC progression, angiogenesis and poor prognosis, suggesting that LAPTM4B protein could be applied not only in predicting patient's outcome, but also in antiangiogenic therapy as a possible novel target molecule.

Background Sirtuin1 (SIRT1) is an NAD+-dependent type III histone deacetylase (HDAC). This research investigated the prevalence of SIRT1 protein expression and its prognostic influence with the aim of validating its potential role in lymphangiogenesis and lymphovascular invasion (LVI) in pN0 esophageal squamous cell carcinoma (ESCC). Methods A total of 206 patients were enrolled in this retrospective study. SIRT1 and VEGF-C protein expression was detected by immunohistochemical staining. Peritumoral lymphatic microvessel density (LVD) and LVI were evaluated by immunostaining for D2-40. Statistical analysis was then preformed to investigate the relevance of SIRT1 expression and various clinicopathologic features and to examine the effect of SIRT1 on tumor-induced lymphangiogenesis, LVI and prognosis. Results SIRT1 positive expression was identified in 95 cases in the nucleus and was significantly correlated with T status (P

The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) is believed to be a promising candidate for cancer gene therapy, yet gene therapy strategies to tackle this disease systemically are often impaired by inefficient delivery of the vector to the tumor tissue. Mesenchymal stem cells (MSCs) have been shown to home to tumor sites and could potentially act as a shield and vehicle for an antitumor gene therapy vector. Here, we used an adenoviral vector expressing TRAIL to transduce MSCs and studied the apoptosis-inducing activity of these TRAIL-carrying MSCs on esophageal cancer cell Eca-109. Our results showed that, in vitro, TRAIL-expressing MSCs were able to inhibit proliferation and induce apoptosis in Eca-109 cells by an MTT assay, co-culture experiments and flow cytometry analysis. In vivo, TRAIL-expressing MSCs also displayed an ability to inhibit tumor growth in an Eca-109 xenograft mouse model. Together, our findings indicated that the gene therapy strategy of MSCs-based TRAIL gene delivery has a wide potential value for improving the treatment of esophageal cancer.

In this study, we found that increased BRF2 protein expression was prevalent in NSCLC. Overexpression of BRF2 correlated with abnormal expression of E-cadherin, N-cadherin, and snail. Additionally, expression of BRF2 was found to be an independent prognostic factor in NSCLC patients. Furthermore, we showed that targeted knockdown of BRF2 expression could inhibit the migratory and invasive abilities of NSCLC cells and induced loss of the epithelial-mesenchymal transition of NSCLC cells. These results suggested that BRF2 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting epithelial-mesenchymal transition (EMT) program.