Identification and immunological characteristics of anoikis-associated molecular clusters in lung adenocarcinoma.

Anoikis plays a crucial role in the progression, prognosis, and immune response of lung adenocarcinoma (LUAD). However, its specific impact on LUAD remains unclear. In this study, we investigated the intricate interplay of nesting apoptotic factors in LUAD. By analyzing nine key nesting apoptotic factors, we categorized LUAD patients into two distinct clusters. Further examination of immune cell profiles revealed that Cluster A exhibited greater infiltration of innate immune cells than did Cluster B. Additionally, we identified two genes closely associated with prognosis and developed a predictive model to differentiate patients based on molecular clusters. Our findings suggest that the loss of specific anoikis-related genes could significantly influence the prognosis, tumor microenvironment, and clinical features of LUAD patients. Furthermore, we validated the expression and functional roles of two pivotal prognostic genes, solute carrier family 2 member 1 (SLC2A1) and sphingosine kinase 1 (SPHK1), in regulating tumor cell viability, migration, apoptosis, and anoikis. These results offer valuable insights for future mechanistic investigations. In conclusion, this study provides new avenues for advancing our understanding of LUAD, improving prognostic assessments, and developing more effective immunotherapy strategies.

SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. METHODS: The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. RESULTS: SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. CONCLUSIONS: SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.

CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer.

Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clinicopathological features of CRC with BRAF V600E mutant or wild type were collected in this study. Immunohistochemistry (IHC) assays were conducted to test the expressions of vascular endothelial growth factor (VEGF), CD31 and CXCL16. ROC curve was used to determine the optimal cut off values of CXCL16. A total of 680 patients including 141 BRAF V600E type and 679 wild type were included. BRAF V600E mutant tumors were presented with significant worse clinicopathological features and a shorter overall survival (OS) than wild-type. Besides, chemokines CXCL16 was up-regulated in BRAF V600E mutant tissues and was associated with poorer prognosis. In addition, VEGF levels and vascular endothelial cell density was significantly increased in BRAF mutation. At last, CXCL16 was positively correlated with VEGF expression and vascular endothelial cell density. In conclusion, BRAF V600E mutations may promote metastasis of CRC by regulating CXCL16 expression and promoting angiogenesis in the TME.

Microwave ablation for the treatment of peripheral ground-glass nodule-like lung cancer: Long-term results from a multi-center study.

Introduction: Microwave ablation (MWA) is an effective and safe approach for the treatment of ground-glass nodule (GGN)-like lung cancer, but long-term follow-up is warranted. Therefore, this multi-center retrospective study aimed to evaluate the results of MWA for the treatment of peripheral GGN-like lung cancer with a long-term follow-up. Materials and Methods: From June 2013 to January 2018, a total of 87 patients (47 males and 40 females, mean age 64.6 ± 10.2 years) with 87 peripheral lung cancer lesions showing GGN (mean long axis diameter, 17 ± 5 mm) underwent computed tomography (CT)-guided percutaneous MWA. All GGN-like lung cancers were histologically verified. The primary endpoints were local progression-free survival (LPFS) and overall survival (OS). The secondary endpoints were cancer-specific survival (CSS) and complications. Results: During a median follow-up of 65 months, both the 3-year and 5-year LPFS rates were 96.6% and 96.6%. The OS rate was 94.3% at 3 years and 84.9% at 5 years, whereas the 3-year and 5-year CSS rates were 100% and 100%, respectively. No periprocedural deaths were observed. Complications were observed in 49 patients (51.6%). Grade 3 or higher complications included pneumothorax, pleural effusion, hemorrhage, and pulmonary infection, which were identified in ten (10.5%), two (2.1%), two (2.1%), and one (1.1%) patient, respectively. Conclusions: CT-guided percutaneous MWA is an effective, safe, and potentially curative treatment regimen for GGN-like lung cancer.

Experimental study on the accuracy of non-invasive temperature measurement by magnetic resonance in microwave ablation.

Aims: This study aimed to explore the accuracy of non-invasive temperature measurement based on proton resonance frequency (PRF) phase subtraction in microwave ablation (MWA). Methods and Material: The signal change of the agar phantom during the ablation process was monitored by the gradient echo sequence under 1.5 T superconducting magnetic resonance imagining (MRI), and the temperature change was converted by the phase subtraction method of the PRF, which was compared with the temperature measured using an optical fiber. Statistical Analysis Used: SPSS software version 22.0 was used for data processing, and the independent sample t-test was used for comparative analysis. P < 0.05 indicated statistical significance. Results: The maximum error between the MRI temperature measurement and the standard value was 3.61°C, whereas the minimum and average errors were 0.01°C and 1.19°C ± 0.78°C, respectively. Conclusions: The temperature measurement technology, which is based on the PRF phase method, has good accuracy in MRI-guided MWA.

Microwave ablation therapy assisted by artificial pneumothorax and artificial hydrothorax for lung cancer adjacent to the vital organs.

Objectives: This study aimed to investigate the technical methods and safety of artificial pneumothorax and artificial hydrothorax in the treatment of lung cancer adjacent to vital organs by CT-guided microwave ablation. Subjects and Methods: Three of the six patients were men and three were women, with a mean age of 66.0 years (range 47-78 years). There patients had primary pulmonary adenocarcinoma, one had lung metastasis from liver cancer, one had lung metastasis from colon cancer, and one had lung metastasis from bladder cancer. There were four patients with a single lesion, one with two lesions, and one with three lesions. The nine lesions had a mean diameter of 1.1 cm (range 0.4-1.9). In three patients, the lung cancer was adjacent to the heart, and in the remaining three, it was close to the superior mediastinum. Six patients were diagnosed with lung cancers or lung metastases and received radical treatment with microwave ablation (MWA) assisted by artificial pneumothorax and artificial hydrothorax in our hospital. Postoperative complications were observed and recorded; follow-up was followed to evaluate the therapeutic effect. Results: The artificial pneumothorax and artificial hydrothorax were successfully created in all six patients. A suitable path for ablation needle insertion was also successfully established, and microwave ablation therapy was carried out. 2 patients developed pneumothorax after operation; no serious complications such as operation-related death, hemothorax, air embolism and infection occurred.Moreover, 4-6 weeks later, an enhanced CT re-examination revealed no local recurrence or metastasis, and the rate of complete ablation was 100%. Conclusions: Microwave ablation, assisted by artificial pneumothorax, artificial hydrothorax, is a safe and effective minimally invasive method for treating lung cancer adjacent to the vital organs, and optimizing the path of the ablation needle and broadening the indications of the ablation therapy.

The correlation between multimodal radiomics and pathology about thermal ablation lesion of rabbit lung VX2 tumor.

Objective: To explore the correlation of CT-MRI pathology with lung tumor ablation lesions by comparing CT, MRI, and pathological performance of rabbit lung VX2 tumor after thermal ablation. Methods: Thermal ablation including microwave ablation (MWA) and radiofrequency ablation (RFA) was carried out in 12 experimental rabbits with lung VX2 tumors under CT guidance. CT and MRI performance was observed immediately after ablation, and then the rabbits were killed and pathologically examined. The maximum diameter of tumors on CT before ablation, the central hypointense area on T2-weighted image (T2WI) after ablation, and the central hyperintense area on T1-weighted image (T1WI) after ablation and pathological necrosis were measured. Simultaneously, the maximum diameter of ground-glass opacity (GGO) around the lesion on CT after ablation, the surrounding hyperintense area on T2WI after ablation, the surrounding isointense area on T1WI after ablation, and the pathological ablation area were measured, and then the results were compared and analyzed. Results: Ablation zones showed GGO surrounding the original lesion on CT, with a central hypointense and peripheral hyperintense zone on T2WI as well as a central hyperintense and peripheral isointense zone on T1WI. There was statistical significance in the comparison of the maximum diameter of the tumor before ablation with a central hyperintense zone on T1WI after ablation and pathological necrosis. There was also statistical significance in the comparison of the maximum diameter of GGO around the lesion on CT with the surrounding hyperintense zone on T2WI and isointense on T1WI after ablation and pathological ablation zone. There was only one residual tumor abutting the vessel in the RFA group. Conclusions: MRI manifestations of thermal ablation of VX2 tumors in rabbit lungs have certain characteristics with a strong pathological association. CT combined with MRI multimodal radiomics is expected to provide an effective new method for clinical evaluation of the immediate efficacy of thermal ablation of lung tumors.

MR-Guided Microwave Ablation for Lung Malignant Tumor: A Single Center Prospective Study.

Objectives: To prospectively investigate the feasibility and efficacy of MRI-guided MWA for lung malignant tumor in our single center. Materials and Methods: 22 patients [mean age, 56.86 ± 13.05(23-73)years] with 23 malignant lung tumors were enrolled in the study. 21 patients had a single lesion and 1 patient had 2 lesions in the ipsilateral lung. The average maximum diameter of the lesion was 1.26 ± 0.65 (0.50-2.58)cm. Percutaneous MWA was guided by 1.5T MRI scanner using a MR-compatible microwave antenna to the target the lung lesions and ablation area was monitored intraoperatively by using a shielded MR-compatible microwave device and then follow-up. Results: All patients were successfully treated under MR-guided MWA for lung tumors. Average operation time was 72.21 ± 24.99 (36-158) mins. T2WI signal intensity of the lesion gradually decreased over the course of MWA. The center of the ablated zones showed a short T1 and short T2 signals with the ring-like of long T1 and long T2 signals surrounded after immediately evaluation. No serious complications occurred. The average follow-up period was 12.89 ± 4.33 (2.0-19.6) months. Local recurrence occurred in one patient, representing a technical efficacy of 95.5% (21/22). Conclusion: Magnetic resonance-guided microwave ablation for lung malignant tumor was feasible and demonstrated unique advantages in efficacy evaluation.

Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation.

Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P=0.001), TNM stage (P=0.001), MSI (P=0.008), and Braf V600E mutation (P=0.001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0.001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.001), lymph node metastasis (P=0.002), TNM stage (P=0.002), MSI (P=0.039), and Braf V600E mutation (P=0.009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0.039, and 0.001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.

Phrenic nerve injury after the percutaneous microwave ablation of lung tumors: A single-center analysis.

Objective: This study aimed to analyze the cases of phrenic nerve injury caused by the percutaneous microwave ablation of lung tumors conducted at our center and to explore the risk factors. Materials and Methods: The data of 455 patients who underwent the percutaneous microwave ablation of lung tumors at the Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University from July 2017 to October 2021, were retrospectively analyzed. The cases of phrenic nerve injury after the percutaneous ablation were reported to analyze the risk factors involved, such as the shortest distance between tumor margin and phrenic nerve, tumor size, and ablation energy. The groups were divided based on the shortest distance between the tumor edge and the phrenic nerve into group 1, d ≤ l cm; group 2, 1 < d ≤2 cm; and group 3, d >2 cm. Lesions with a distance ≤2 cm were compared in terms of tumor size and ablation energy. Results: Among the 455 patients included in this study, 348 had primary lung cancer, and 107 had oligometastatic cancer. A total of 579 lesions were detected, with maximum diameter of 1.27 ± 0.55 cm, and the ablation energy was 9,000 (4,800-72,000) J. Six patients developed phrenic nerve injury, with an incidence of 1.32%. For these six patients, the shortest distance from the lesion edge to the phrenic nerve was 0.75 ± 0.48 cm, and the ablation energy was 10,500 (8,400-34,650) J. There were statistically significant differences in phrenic nerve injury among groups 1, 2, and 3 (P < 0.05). In patients with a distance (d) ≤ 2 cm, there were no significant differences in tumor diameter and energy between the phrenic nerve injury group and the non-injury group (P = 0.80; P = 0.41). In five out of six patients, the diaphragm level completely recovered to the pre-procedure state, and the recovery time of the phrenic nerve was 9.60 ± 5.60 months. Another one was re-examined 11 months after the procedure, and the level of the diaphragm on the affected side had partially recovered. Conclusions: Phrenic nerve injury is a rare but not negligible complication of thermal ablation and is more likely to occur in lesions with a distance ≤2 cm from the phrenic nerve.

Magnetic resonance-guided thermal ablation for small liver malignant tumor located on segment II or IVa abutting the heart: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the clinical safety and efficacy magnetic resonance (MR)-guided percutaneous thermal ablation for the treatment of small liver malignant tumors of segment II and IVa (≤3.0 cm) abutting the heart. METHOD: The enrollment of 24 patients with 25 malignant liver lesions located on the II or IVa segment abutting the heart who underwent MRI-guided thermal ablation between August 2010 and February 2020 were retrospectively analyzed. Follow-up MRI was performed to evaluate the curative effect. Local tumor progression-free survival and overall survival rates were also calculated. RESULTS: The procedures including radiofrequency ablation (RFA) for 15 patients and microwave ablation (MWA) for 9 patients were successfully accomplished (technical success rate of 100%) without major complications. The mean duration time was 78.4 ± 29.4 min (40-140 min), and mean follow-up time was 31.5 ± 22.2 months (6-92 months). The technical efficacy was 100% following one ablation session with MRI assessment after one month. Local tumor progression was observed in one patient with a metastatic lesion located in segment II at 18 months follow-up. The progression-free survival time was 20.1 ± 16.9 months (median: 15 months). The 1-, 3-, and 5-year local tumor progression-free survival rates of this patient were 100%, 94.7%, and 94.7%, respectively. With regards to all the patients, the 1-, 3-, and 5-year estimated overall survival rates were 91.7%, 80.6%, and 50.1%, respectively. CONCLUSION: MR-guided thermal ablation is safe and effective for the treatment of small liver malignant tumors located on the II or IVa segment abutting the heart.

Effects of non-driving related tasks on readiness to take over control in conditionally automated driving.

OBJECTIVE: At conditionally automated driving, the driver can temporarily engage in non-driving related tasks (NDRTs). However, they must safely take over control when the automated driving system reaches its operation limit. Thus, understanding the effects of the NDRTs on driver take-over performance is essential. The present work investigates the effects of various NDRTs on motor readiness in take-over scenarios during conditionally automated driving. METHODS: Three driving simulator studies were conducted. 48, 49, and 22 participants were recruited in three experiments, respectively. The participants were distracted by different NDRTs (everyday task in Experiment 1, arrow task in Experiment 2, and SuRT in Experiment 3) on a tablet mounted in the vehicle. The everyday task included reading the news and watching a video, and the arrow task included a set of arrow matrices presented to the participants in sequence. The time budgets in Experiment 1 included 3 s, 4 s, and 5 s, and the time budgets in Experiment 2 and 3 included 5 s and 7 s. A take-over request (TOR) warning was issued in the automated driving condition when the participants encountered a broken-down car in front. The participants must regain control of the vehicle with the given time budget. The hands-on time was evaluated, measuring the time from the TOR until the hands touch the steering wheel. RESULTS: The task (arrow task and SuRT), time budget (5 s and 7 s), and gender did not affect the hands-on time. However, the hands-on time for the drivers with the everyday task was significantly shorter than that for the drivers with the arrow task in the 5 s time budget. CONCLUSIONS: In conditionally automated driving, the arrow task and SuRT imposed a similar workload on readiness to take over control. Compared to the everyday task, the engagement in the arrow tasks consumed more workload on readiness to take over control.

Efficacy of afatinib in a patient with rare EGFR (G724S/R776H) mutations and amplification in lung adenocarcinoma: A case report.

BACKGROUND: The most common EGFR mutations are in-frame deletions in exon 19 and point mutations in exon 21. Cases with classical EGFR mutations show a good response to EGFR tyrosine kinase inhibitors (TKIs), the standard first-line treatment. With the development of next generation sequencing, some uncommon genomic mutations have been detected. However, the effect of TKIs on such uncommon EGFR mutations remains unclear. CASE SUMMARY: Here, we report a case of rare EGFR co-mutation in non-small cell lung cancer and the efficacy of afatinib on this EGFR co-mutation. A 64-year-old woman was diagnosed with thoracolumbar and bilateral local rib bone metastases, bilateral pulmonary nodules, and pericardial and left pleural effusion. The pathological diagnosis was lung adenocarcinoma. To seek potential therapeutic regimens, rare co-mutation comprising rare EGFR G724S/R776H mutations and amplification were identified. The patient experienced a significant clinical response with a progression-free survival of 17 mo. CONCLUSION: A case of non-small cell lung cancer with rare EGFR G724S/R776H mutations and EGFR amplification responds well to TKI treatment.

Imaging features of microwave-ablated lesions of the VX2 tumors in rabbit lungs on computed tomography and magnetic resonance images and their correlations with pathological examination.

PURPOSE: This study aimed to explore the accuracy of different imaging methods for lesion volume estimation pre- and post-microwave ablation (MWA) as compared with that of pathological examination. METHODS: We used the VX2 cell line to establish the VX2 lung tumor model in rabbits, followed by MWA of the tumor. The imaging features of the VX2 tumors were documented. The volume of the tumors and the ablated lesions were measured and compared across imaging methods, using the pathological examination as reference. RESULTS: Tumors were successfully developed in 11 rabbits (age, 13.91 ± 1.38 weeks; weight, 2.15 ± 0.56 kg). The mean volume of the tumors was 2.05 ± 1.88 cm3. CT showed the strongest correlation with the pathologic examination results (r = 0.998, p<.001). MWA created three-layered structures that were delineated on MRI. The mean volume of the post-ablation lesion was 10.39 ± 8.93 cm3, and the measurement of the post-ablation volume on 3D-VIBE-T1WI showed the strongest correlation with the pathologic examination results (r = 0.991, p<.001). CONCLUSION: Both CT and MRI are capable of depicting lung tumors. In terms of post-ablation evaluation, MR images could provide more versatile information. The 3D-VIBE-T1WI sequence provides more precise lesion volume evaluation after ablation compared with other methods.

Feasibility and efficacy study of microwave ablation of recurrent small HCC guided by enhanced liver-specific magnetic resonance imaging contrast agent.

OBJECTIVES: To investigate the feasibility and efficacy of liver-specific magnetic resonance imaging (MRI) with gadolinium-containing contrast agent guidance for microwave ablation (MWA) of recurrent small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The Ethics Committee of the First Affiliated Hospital of Fujian Medical University approved this study. Eighteen patients presented with 30 recurrent small HCCs, at least one lesion per patient was undetectable on unenhanced MRI, but this was clearly demonstrated in the hepatobiliary phase after liver-specific MRI contrast agent administration. Gd-BOPTA (16 cases) or Gd-EOB-DTPA (2 cases) were injected half an hour before the procedure, and MWA was performed by percutaneous puncture of the target lesion with a magnetic resonance-compatible microwave antenna under 1.5 T MRI guidance. RESULTS: The technical success rate was 100%. The mean maximum diameter of the lesions was 9.7 ± 2.8 mm (5.0-15.4 mm). The mean follow-up time was 11.6 ± 4.7 months (range, 4-19 months), and no local recurrence was observed. CONCLUSIONS: MWA of small HCCs guided by enhanced liver-specific MRI contrast agent is a safe and effective technique.

Understanding take-over performance of high crash risk drivers during conditionally automated driving.

Understanding driver behavior of conditionally automated driving is necessary to ensure a safe transition from automated to manual driving. This study aimed to examine the difference in take-over performance between high crash risk (HCR) and lower crash risk (LCR) drivers in emergency take-over situations during conditionally automated driving. In the current simulator study, a 3 × 3 (within-subjects) factorial design was used, including the task factors (no task, reading the news, and watching a video) and time budget factors (time budget = 3 s, 4 s, and 5 s). Forty-eight participants completed a test drive on an approximately 10 km long two-way six-lane urban road. The participants firstly were in manual control and then switched to the automated driving mode at a speed of 50 km/h. The automated driving system was able to detect a broken car in the ego-lane and requested the driver to take over the control of the vehicle. There are at least one or two other vehicles or motorcycles on each side of the ego-vehicle, resulting in fewer escape paths. For the two non-handheld non-driving-related tasks (NDRTs), the participants were asked to be fully engaged in a task without any need to monitor the road environments. Each participant completed nine emergency take-over situations. The participants were classified into two groups that were labeled LCR (N ≤ 2) and HCR drivers (N ≥ 3) according to the number of accidents per driver. The results show that LCR drivers had shorter brake reaction time compared to HCR drivers. For all drivers, the engagement in a task led to longer response times, and the time budget affected the longitudinal vehicle control. In addition, the task affected the response times for LCR and HCR drivers, but only the time budget affected the longitudinal vehicle control for LCR drivers. For all drivers, LCR and HCR drivers, the time budget and task affected the safety of take-over. Especially, the two non-handheld everyday tasks seem to have a similar effect on the drivers' workload. Therefore, the HCR drivers had a lower hazard perception compared to the LCR drivers, and the factor regarding the individual difference of driving ability in take-over situations should be considered to design safe take-over concepts for automated vehicles.

NLK interacts with 14­3­3ζ to restore the expression of E­cadherin.

The Nemo­like kinase (NLK), a conserved serine/threonine kinase, plays a critical role in the regulation of a variety of transcription factors, with important roles in determining cell fate. Although recent studies have demonstrated decreased expression patterns of NLK in various types of human cancer, the functional mechanism of NLK in cancer development has not been elucidated. Here, in the present study overexpression of NLK was found to inhibit the growth and migration of the non­small cell lung cancer A549 cell line. NLK was subsequently found to interact with 14­3­3ζ (also known as YWHAZ), which is responsible for E­cadherin silencing during epithelial­mesenchymal transition (EMT). Furthermore, NLK overexpression was able to restore the expression of E­cadherin inhibited by 14­3­3ζ. Notably, NLK interacts with 14­3­3ζ and prevents its dimerization, which is essential for 14­3­3ζ stability and function. By fusing two copies of the 14­3­3ζ gene, via a Gly­rich linker, a non­dissociable dimer of 14­3­3ζ was formed. It was found that NLK was unable to restore the expression of E­cadherin inhibited by the overexpression of the fused dimer of 14­3­3ζ. In addition, the increased ability of migration induced by the overexpression of fused 14­3­3ζ dimer could not be altered by NLK overexpression. The results from the present study indicate that NLK is a negative regulator of 14­3­3ζ and plays a tumor suppressive role in the inhibition of cancer cell migration.

Percutaneous radiofrequency ablation for small hepatocellular carcinoma in hepatic dome under MR-guidance: clinical safety and efficacy.

Purpose: To evaluate the clinical safety and efficacy of percutaneous radiofrequency ablation (RFA) using multitined expandable electrodes under magnetic resonance imaging (MRI) guidance in the treatment of small hepatocellular carcinomas (HCCs) in the hepatic dome.Materials and methods: The data of 49 patients with 50 HCC lesions in the hepatic dome who underwent MRI-guided RFA from April 2010 to January 2018 were retrospectively analyzed. Planning, targeting, and controlling were performed under MR-guidance during the procedure. The complications after RFA were observed. Follow-up MRI was performed to evaluate the curative effect. The local progression-free survival, recurrence-free survival, and overall survival rates were calculated using the Kaplan-Meier survival curve.Results: The procedures were successfully accomplished in all patients without major complications. The mean follow-up time was 36.9 ± 25.8 months (range, 3-99 months). Technical success was 100% after one RFA session with MRI assessment after 1 month. Local tumor progression was observed in one patient (2%) with the lesion located in the hepatic dome at 4 months on a subsequent follow-up MRI. The progression-free survival time was 25.0 ± 22.7 months (median, 17.0 months). The 1-,3-, and 5-year local tumor progression-free survival rates were all 98.0%. The 1-,3-, and 5-year recurrence-free survival rates were 68.1%, 39.9%, and 28.5%, respectively, and the estimated overall survival rates were 93.7%, 76.3%, and 54.3%, respectively.Conclusion: Planning, targeting, and controlling of RFA were well supported by MRI with acceptable time. MRI-guided RFA for small HCCs in the hepatic dome is safe and effective with fewer RF sessions.

High Quantum Efficiency Hot Electron Electrochemistry.

Using hot electrons to drive electrochemical reactions has drawn considerable interest in driving high-barrier reactions and enabling efficient solar to fuel conversion. However, the conversion efficiency from hot electrons to electrochemical products is typically low due to high hot electron scattering rates. Here, it is shown that the hydrogen evolution reaction (HER) in an acidic solution can be efficiently modulated by hot electrons injected into a thin gold film by an Au-Al2O3-Si metal-insulator-semiconductor (MIS) junction. Despite the large scattering rates in gold, it is shown that the hot electron driven HER can reach quantum efficiencies as high as ∼85% with a shift in the onset of hydrogen evolution by ∼0.6 V. By simultaneously measuring the currents from the solution, gold, and silicon terminals during the experiments, we find that the HER rate can be decomposed into three components: (i) thermal electron, corresponding to the thermal electron distribution in gold; (ii) hot electron, corresponding to electrons injected from silicon into gold which drive the HER before fully thermalizing; and (iii) silicon direct injection, corresponding to electrons injected from Si into gold that drive the HER before electron-electron scattering occurs. Through a series of control experiments, we eliminate the possibility of the observed HER rate modulation coming from lateral resistivity of the thin gold film, pinholes in the gold, oxidation of the MIS device, and measurement circuit artifacts. Next, we theoretically evaluate the feasibility of hot electron injection modifying the available supply of electrons. Considering electron-electron and electron-phonon scattering, we track how hot electrons injected at different energies interact with the gold-solution interface as they scatter and thermalize. The simulator is first used to reproduce other published experimental pump-probe hot electron measurements, and then simulate the experimental conditions used here. These simulations predict that hot electron injection first increases the supply of electrons to the gold-solution interface at higher energies by several orders of magnitude and causes a peaked electron interaction with the gold-solution interface at the electron injection energy. The first prediction corresponds to the observed hot electron electrochemical current, while the second prediction corresponds to the observed silicon direct injection current. These results indicate that MIS devices offer a versatile platform for hot electron sources that can efficiently drive electrochemical reactions.

Cyclin A1 is associated with poor prognosis in oesophageal squamous cell carcinoma.

Dysregulation of cyclin A1 (CCNA1) is implicated in the carcinogenesis, progression and metastasis of many types of solid tumours. In the present study, an mRNA single-channel expression profile chip experiment revealed that the CCNA1 mRNA levels in oesophageal squamous cell carcinoma (ESCC) were increased >10-fold compared with those in the adjacent non-cancer tissues. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry analyses were performed to additionally investigate the role of CCNA1 in the development and progression of ESCC in patients treated by radical resection of the oesophagus. The association between CCNA1 mRNA expression and the clinicopathological parameters of patients with ESCC was statistically analysed. The results indicated that upregulation of CCNA1 occurred in ~70% of patients with ESCC, and increased CCNA1 mRNA expression was significantly associated with advanced clinical stage, lymph node metastasis, invasiveness and poor clinical outcome, including disease-free survival and overall survival rates. Taken together, the data suggested that CCNA1 had an important function in ESCC development and progression, and may serve as a prognostic biomarker and therapeutic target in ESCC.