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BackgroundThere are no optimal regimens for advanced thymic epithelial tumors (TETs) when front-line chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with routine chemotherapeutic regimen.MethodsPatients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160mg/m2) or cisplatin (70mg/m2) and carboplatin (area under the curve, 6) plus Bevacizumab (7.5mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred.ResultsBetween March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years).The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression free survival for thymoma and thymic carcinoma were 6 and 8 months, respectively. Hematological toxicities were the main side effects.ConclusionsPaclitaxel and platinum plus Bevacizumab showed promising effect in refractory or relapsed advanced TETs without severe toxicity. Even applied as salvage therapy, this regimen resulted in better ORR than the front-line chemotherapy.

Precise point positioning (PPP) is receiving increasing interest due to its cost-effectiveness, global coverage and high accuracy. However, its application in the urban environment is still full of challenges due to the satellite tracking sky-view. Thus, we presented a comprehensive positioning model by fusing the multi-GNSS (global navigation satellite system) combination, GNSS/INS (inertial navigation system) tightly coupled integration as well as the ionospheric and tropospheric augmentation in the undifferenced and uncombined PPP. The performance of this model in dual-frequency and single-frequency positioning was assessed with two experiments that denoted as T019 and T023, respectively, and both the experiments were carried out in a real urban environment. Particularly, the experiment T023 was carried out in the Second Ring Road of Wuhan city, which can be regarded as a typical downtown environment. Concerning the regional atmospheric augmentation, observations from 5 reference stations with an inter-station distance of about 40 km were also collected during the experimental time. The comparison between reference stations suggested that the regional tropospheric model had a precision of better than 0.6 cm in terms of zenith tropospheric delay, while the regional ionospheric model had a precision of around 0.5 total electron content unit in terms of Vertical Total Electron Content. It can be concluded that the GPS-only PPP can be improved significantly for urban vehicle navigation with these techniques, i.e., the multi-GNSS, INS tightly coupled integration and the atmospheric augmentation, through the positioning analysis, while INS tightly coupled integration makes the most contributions under the downtown environment, and the improvement of the regional atmospheric augmentation in single-frequency PPP is more significant since that single frequency is more sensitive to the ionospheric delay. In addition, it is proved that the regional atmospheric augmentation accelerates positioning convergence. The 3D positioning root-mean-square (RMS) with the comprehensive positioning model for dual frequency are 0.22 m and 0.77 m for T019 and T023, respectively. Concerning single-frequency PPP, the 3D RMS is 0.45 m and 1.17 m for T019 and T023, respectively. Moreover, taking the lane-level navigation under the downtown environment of T023 into consideration, we further presented the cumulative frequency of the horizontal positioning error less than 1 m, i.e., $$P\left( {\sqrt {{\text{d}}N^{2} + {\text{d}}E^{2} } < 1\;{\text{m}}} \right)$$ , and the best solution can be found with PPP by fusing all the techniques, in which $$P\left( {\sqrt {{\text{d}}N^{2} + {\text{d}}E^{2} } < 1\;{\text{m}}} \right)$$ is 99.0% and 93.2% for dual frequency and single frequency, respectively.

Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.

The correlations between histological, clinical features and prognosis of stage I invasive mucinous adenocarcinoma (IMA) have not been thoroughly studied for its rare incidence. This study aimed to compare the prognosis among IMA with different percentage of mucinous component and the effect of adjuvant chemotherapy on IMA patients. A total of 145 stage I IMA and 3536 invasive nonmucinous adenocarcinoma patients with R0 resection were included. Based on the percentage of mucinous pattern presented in tumor, IMA were classified into two subgroups: pure mucinous (>90 % invasive mucinous pattern) and mixed mucinous/nonmucinous (≥10 % of each histologic component). Invasive nonmucinous adenocarcinomas were classified into three subgroups: lepidic (LEP), acinar/papillary (ACN/PAP) and solid/micropapillary (SOL/MIP). Disease-free survival (DFS) and overall survival (OS) were assessed and compared among IMA and invasive nonmucinous patients. For IMA patients, DFS (p = 0.003) was worse for mixed mucinous/nonmucinous compared with pure mucinous subgroup, OS (p = 0.514) was not prognostically different between two groups. There were no significant difference for DFS (p = 0.428) and OS (p = 0.232) between IMA and invasive nonmucinous adenocarcinoma. However, statistical significance were seen for DFS (p

NF-κB signaling plays very important role in the tumorigenesis of nonsmall cell lung cancer (NSCLC). However, the molecular mechanisms for the dysregulation of NF-κB signaling in NSCLC have not been fully understood. In the previous reports, we have showed that large tumor suppressor gene 2 (LATS2) inhibited NF-κB signaling in NSCLC cells, whereas the details for the mechanism remain unknown. Here, we reported that LATS2 is a suppressor of tumor necrosis factor (TNF-α)-induced NF-κB signaling by inhibiting the interaction between TAK1 and IKKβ. Overexpression of LATS2 largely blocked TNF-α-induced NF-κB activation and IκBα degradation, whereas knockdown of LATS2 showed the opposing results. Mechanistically, we identified that LATS2 interacted with IKKβ and blocked the interaction between IKKβ and TAK1. Our results indicate that LATS2 functions as a pivotal negative regulator in TNF-α-induced activation of NF-κB via disrupting the interaction of TAK1 with IKKβ.

LATS2 (Large tumor suppressor) has been reported to be dys-regulated in several cancer types. However, its function in non-small cell lung cancer (NSCLC) remains poorly understood. Here, it was found that the expression level of LATS2 was decreased in NSCLC tissues. Moreover, forced expression of LATS2 in NSCLC cells inhibited cell growth and migration, while knockdown of the expression of LATS2 promoted the tumorigenicity of NSCLC cells. Mechanistically, LATS2 was found to negatively regulate NF-κB signaling in NSCLC cells. Taken together, our study suggested that down-regulation of LATS2 was very important in the progression of NSCLC, and restoring the function of LATS2 might be a promising therapeutic strategy for NSCLC.

Background Despite increasingly radical surgery for esophageal carcinoma, many patients still develop tumor recurrence after operation. This study was designed to analyze the clinical and pathologic influencing factors of early recurrence in patients with histological node-negative (pN0 stage) esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. Methods A retrospective study on 112 consecutive pN0 stage ESCC patients who underwent esophagectomy with lymphadenectomy by the same surgical team from January 2004 to December 2010. There were 92 male and 20 female patients, aging from 36 to 80 years with a mean age of 60.3 years. The Cox proportional hazards model was used to determine the independent risk factors for recurrence within 3 years after the operation. Results Recurrence was recognized in 45 patients (40.2%) within 3 years after operation. The median time to tumor recurrence was 17.4 months. Locoregional recurrence was found in 38 patients (33.9%) and hematogenous metastasis in 7 patients (6.3%). However, locoregional recurrence accounted for 84.4% of all relapse patients. Recurrence closely correlated with tumor location, grade of differentiation, primary tumor stage (pT) and pathologic stage (χ2 = 6.380 to 18.837, p < 0.05). The Cox multivariate analysis showed that upper/middle thoracic location (OR = 1.092, p = 0.049) and pT3-4a stage (OR = 3.296, p = 0.017) were independent risk factors for postoperative locoregional recurrence. Conclusion Locoregional recurrence was the most common recurrence pattern of patients with pN0 ESCC within 3 years after operation. Upper/middle thoracic location and pT3-4a stage were independent risk factors for locoregional recurrence of pN0 ESCC after radical esophagectomy. Electronic supplementary material The online version of this article (doi:10.1186/s13019-014-0150-4) contains supplementary material, which is available to authorized users.