A preliminary study of modified inflatable mediastinoscopic and single-incision plus one-port laparoscopic esophagectomy.

Background: Esophageal malignancies have a high morbidity rate worldwide, and minimally invasive surgery has emerged as the primary approach for treating esophageal cancer. In recent years, there has been increasing discussion about the potential of employing inflatable mediastinoscopic and laparoscopic approaches as an option for esophagectomy. Building on the primary modification of the inflatable mediastinoscopic technique, we introduced a secondary modification to further minimize surgical trauma. Methods: We conducted a retrospective analysis of patients who underwent inflatable mediastinoscopy combined with laparoscopic esophagectomy at the Second Affiliated Hospital of Naval Medical University from March 2020 to March 2023. The patients were allocated to the following two groups: the traditional (primary modification) group, and the secondary modification group. Operation times, intraoperative bleeding, and postoperative complications were compared between the groups. Results: The procedure was successfully performed in all patients, and conversion to open surgery was not required in any case. There were no statistically significant differences in the surgical operation time, intraoperative bleeding, number of dissected lymph nodes, and rate of postoperative anastomotic leakage between the two groups. However, a statistically significant difference was observed in the length of the mobilized esophagus between the two groups. The mobilization of esophagus to the level of diaphragmatic hiatus via the cervical incision was successfully achieved in more patients in the secondary modification group than the primary modification group. Conclusions: Inflatable mediastinoscopy combined with single-incision plus one-port laparoscopic esophagectomy is a safe and effective surgical procedure. The use of a 5-mm flexible endoscope, ultra-long five-leaf forceps, and LigaSure Maryland forceps facilitates esophageal mobilization and lymph node dissection through a single cervical incision.

Magnolol promotes the autophagy of esophageal carcinoma cells by upregulating HACE1 gene expression.

Esophagus cancer (EC) is one of the most aggressive malignant digestive system tumors and has a high clinical incidence worldwide. Magnolol, a natural compound, has anticancer effects on many cancers, including esophageal carcinoma, but the underlying mechanism has not been fully elucidated. Here, we first find that magnolol inhibits the proliferation of esophageal carcinoma cells and enhances their autophagy activity in a dose- and time-dependent manner. This study demonstrates that magnolol increases the protein levels of LC3 II, accompanied by increased HACE1 protein levels in both esophageal carcinoma cells and xenograft tumors. HACE1-knockout (KO) cell lines are generated, and the ablation of HACE1 eliminates the anti-proliferative and autophagy-inducing effects of magnolol on esophageal carcinoma cells. Additionally, our results show that magnolol primarily promotes HACE1 expression at the transcriptional level. Therefore, this study shows that magnolol primarily exerts its antitumor effect by activating HACE1-OPTN axis-mediated autophagy. It can be considered a promising therapeutic drug for esophageal carcinoma.

Different gene alterations in patients with non-small-cell lung cancer between the eastern and southern China.

Geographical differences are conspicuous in lung cancer, and the distinct molecular features of lung tumor between Western patients and Asian patients have been demonstrated. However, the etiology of non-small-cell lung cancer (NSCLC) and the distribution of associated molecular aberrations in China have not been fully elucidated. The mutational profiles of 12 lung cancer-related genes were investigated in 85 patients from eastern China and 88 patients from southern China who had been histologically confirmed NSCLC. Overall, 93.6% (162/173) of tumor samples harbored at least one somatic alteration. The most frequently mutated genes were TP53 (56.1%), EGFR (50.3%), and KRAS (14.5%). We found that EGFR mutated much more frequently (60.0% vs 40.9%, P = 0.012) and TP53 mutations had significantly lower incidence (47.1% vs 64.8%, P = 0.019) in eastern cohort than that in southern cohort. Mutational signature analysis revealed a region-related mutagenesis mechanism characterized by a high prevalence of C to T transitions mainly occurring at CpG dinucleotides in southern patients. This study reveals the difference in the mutational features between NSCLC patients in eastern and southern China. The distinct patterns of gene mutation could provide clues for the mechanism of carcinogenesis of lung cancer, offering opportunities to stratify patients into optimal treatment plans based on genomic profiles.

The synergized diagnostic value of VTQ with chemokine CXCL13 in lung tumors.

Virtual Touch Tissue Quantification (VTQ) offers several advantages in the diagnosis of various lung diseases. Chemokine expression levels, such as CXCL13, play a vital role in the occurrence and development of tumors and aid in the diagnosis process. The purpose of this study was to evaluate the combined value of VTQ and changes in CXCL13 expression levels for the diagnosis of lung tumors. A total of 60 patients with thoracic nodules and pleural effusion were included, with 30 of them having malignant pleural effusion (based on pathology) and the remaining 30 having benign thoracic nodules and pleural effusion. The relative expression level of CXCL13 was measured in the collected pleural effusions using Enzyme-Linked Immunosorbent Assay (ELISA). The relationship between CXCL13 expression levels and various clinical features was analyzed. A Receiver Operating Characteristic (ROC) curve analysis was conducted on the VTQ results and relative expression levels of CXCL13, and the areas under the curve, critical values, sensitivity, and specificity were calculated. Multivariate analysis incorporating multiple indicators was performed to determine the accuracy of lung tumor diagnosis. The results showed that the expression levels of CXCL13 and VTQ were significantly higher in the lung cancer group compared to the control group (P < 0.05). In the Non-Small Cell Lung Cancer (NSCLC) group, CXCL13 expression levels increased with later TNM staging and poorer tumor differentiation. The expression level of CXCL13 in adenocarcinoma was higher than that in squamous cell carcinoma. The ROC curve analysis revealed that CXCL13 had an area under the curve (AUC) of 0.74 (0.61, 0.86) with an optimal cut-off value of 777.82 pg/ml for diagnosing lung tumors. The ROC curve analysis of VTQ showed an AUC of 0.67 (0.53, 0.82) with a sensitivity of 60.0% and a specificity of 83.3%, and an optimal diagnostic cut-off of 3.33 m/s. The combination of CXCL13 and VTQ for diagnosing thoracic tumors had an AUC of 0.842 (0.74, 0.94), which was significantly higher than either factor alone. The results of the study demonstrate the strong potential of combining VTQ results with chemokine CXCL13 expression levels for lung tumor diagnosis. Additionally, the findings suggest that elevated relative expression of CXCL13 in cases of malignant pleural effusion caused by non-small cell lung cancer may indicate a poor prognosis. This provides promising potential for using CXCL13 as a screening tool and prognostic indicator for patients with advanced lung cancer complicated by malignant pleural effusion.

A new preoperative localization of pulmonary nodules guided by mixed reality: a pilot study of an animal model.

Background: With the popularity of high-resolution computed tomography (HRCT), more and more pulmonary nodules are being discovered. Video-assisted thoracoscopic surgery (VATS) has become the first choice for surgical treatment of pulmonary nodules. The use of accurate preoperative localization is crucial for successful resection in VATS. At present, there are many kinds of preoperative localization methods, but there are certain disadvantages. This study aimed to evaluate the feasibility and safety of mixed reality (MR)-guided pulmonary nodules localization, which is a new method that can benefit patients to a greater extent. Methods: By constructing an animal model of pulmonary nodules localization, 28 cases of pulmonary nodules were located by MR-guided localization. We recorded the localization accuracy, localization time, insertion attempts, and incidence of complications related to localization under MR-guidance. Results: All 28 nodules were successfully located: the deviation of MR-guided localization was 5.71±2.59 mm, localization time was 8.07±1.44 min, and insertion attempts was 1. A pneumothorax and localizer dislodgement occurred in 1 case, respectively. Conclusions: Since preoperative localization is critical for VATS resection of pulmonary nodules, we investigated a new localization method. As indicated by our study, MR-guided localization of pulmonary nodules is feasible and safe, which is worthy of further research and promotion. We have also registered corresponding clinical trials to further investigate and help to improve our understanding of this technique.

Application of wireless thoracoscopy in thoracic surgery.

To explore the safety and feasibility of wireless thoracoscope in thoracic surgery. A retrospective analysis was made of all the clinical data of 90 patients with thoracoscope lung resection, from April to August 2021, Shanghai changzheng hospital thoracic minimally invasive center. Compared the thoracoscope preparation time, picture resolution, picture delay, surgeon comfort level, assistant comfort level between the wireless thoracoscope group and wired thoracoscope group. The thoracoscopic preparation time of the wireless thoracoscope group was significantly shorter than that of the wired group (26.66 ± 6.04 vs 62.14 ± 10.07, p < 0.0001). Comfort level of the surgeon (4.64 ± 0.48 vs 3.77 ± 0.42, p < 0.001) and the comfort level of the assistant (4.85 ± 0.36 vs 3.88 ± 0.32, p < 0.001) of the wireless thoracoscope group were higher than that of the wired thoracoscope group. There were no statistically significant differences in video sharpness (4.64 ± 0.48 vs 4.74 ± 0.44, p = 0.31). Although there was one case picture delay in wireless group, it was caused by low power which could be dealt with by a good charge before surgery. The wireless thoracoscope has the advantages of short preparation time, high comfort for the surgeon and the assistant, no less than the wired thoracoscope in picture resolution and picture delay. Wireless connection is more convenient and portability, which is worthy of further application in clinical practice.

Clinical comparative study of glasses-free 3D and 2D thoracoscopic surgery in minimally invasive esophagectomy.

Objective: To investigate the safety and efficacy of glasses-free three-dimensional (3D) thoracoscopic surgery in minimally invasive esophagectomy (MIE). Methods: The clinical data of 98 patients, including 81 men and 17 women aged 45-77 years, with esophageal squamous cell carcinoma who underwent minimally invasive thoracoscopic esophagectomy from January 2017 to December 2019 [3 years, with clinical follow-up time: 1 year~4 years (2017.01-2020.12)] were retrospectively analyzed. Patients were divided into two groups according to different surgical methods including a glasses-free 3D thoracoscopic group (G-3D group: 38 patients) and a two-dimesional (2D) thoracoscopic group (2D group: 60 patients). The clinical outcome of the two groups were compared. Results: The operation time of the thoracoscopic part in the G-3D group was significantly shorter than that in the 2D group (P<0.05). The total number of lymph node dissection in the G-3D group was more than that in the 2D group (P<0.05). The thoracic indwelling time, postoperative hospital stay, severe pulmonary infection, arrhythmia, anastomotic leakage, chylothorax, and recurrent laryngeal nerve injury were not significantly different between the two groups (P>0.05). There was also no significant difference between the two groups on the progression-free survival (P>0.05). Conclusion: Glasses-free 3D thoracoscopic surgery for esophageal cancer is a safe and effective surgical procedure. Compared with 2D thoracoscopic MIE, glasses-free 3D thoracoscopic MIE for esophageal cancer has higher safety, more lymph node dissection, and higher operation efficiency through the optimized surgical operations. We believe that glasses-free 3D thoracoscopy for MIE is worthy of clinical promotion.

A New Traceless Technique for Cosmetic Closure of Minimally Invasive Incision and Chest Tube Fixation After Uniportal Video-Assisted Thoracoscopic Surgery.

Background: With uniportal video-assisted thoracoscopic surgery (VATS) becoming mainstream, how to make the incision cosmetic has attracted much attention. This study aimed to introduce a new traceless method for cosmetic closure of the incision and a special procedure for chest tube fixation after uniportal VATS and to evaluate the feasibility, effectiveness, and safety of this new technique. Methods: In this retrospective study, a total of 258 consecutive patients who underwent uniportal VATS were included. Among them, 127 patients were treated with a conventional method, and 131 patients were treated with a new method. Results: Patients in the new method group had a significantly less incidence of subcutaneous emphysema after the chest tube was removed. The incidence of pneumothorax after the chest tube was removed and fat liquefaction of chest incision was not significantly different between the two groups. No differences in the incidence of pneumothorax after chest tube removal and fat liquefaction of postsurgical incision were found between the two groups. Additionally, there was also no significant difference in follow-up items. Conclusions: Taken together, our results showed that this new method for minimally invasive incision closure and chest tube fixation after uniportal VATS was as feasible, effective, and safe as the conventional one but more cosmetic.

Effect Evaluation of Subxiphoid and Intercostal Thymectomy: A Meta-Analysis and Systematic Review.

Background: It still remains unclear whether subxiphoid video-assisted thoracoscopic surgery (SVATS) thymectomy is safe and reasonable. This meta-analysis aims at assessing the effectiveness and safety of SVATS for thymoma in comparison with that of intercostal video-assisted thoracoscopic surgery (IVATS) thymectomy. Methods: All the relevant data systematically analyzed in this thesis were retrieved from PubMed, the Cochrane Library, web of science, EMBASE, and ClinicalTrials.gov. The time span for data retrieval was from the date of database establishment to March 2022. The outcome indicators include operation time, intraoperative blood loss, duration of postoperative drainage, postoperative hospital days, visual analogue scale (VAS) score on the day of operation, VAS score on postoperative day 3, and VAS score on postoperative day 7; postoperative complications were analyzed in our meta-analysis. Results: In 13 studies of this paper, there were 1,198 cases included. Among them, 563 cases were treated by SVATS thymectomy and 635 cases by IVATS thymectomy. There was no significant difference in the operation time [113.38 vs. 119.91  min, 95% confidence interval (CI): -0.70-0.15, p = 0.20) and the incidence of intraoperative and postoperative complications (RR = 0.82, 95% CI: 0.58-1.15, p = 0.25) between SVATS thymectomy and IVATS thymectomy. However, SVATS thymectomy significantly reduced the amount of intraoperative blood loss (47.68 vs. 66.69  mL, SMD = -0.57, 95% CI: -0.95 to -0.18, p = 0.004), postoperative drainage days (2.12 vs. 2.72 days, SMD = -0.46, 95% CI: -0.74 to -0.18, p = 0.001), postoperative hospital stays (4.53 vs. 5.91 days, SMD = -0.64, 95% CI: -0.96 to -0.31, p = 0.0001), and VAS scores after the operation. Discussion: SVATS thymectomy is safe and feasible, and the perioperative effect is better than IVATS thymectomy to a certain extent, which is worthy of popularization and further research.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/.

Transcervical inflatable mediastinoscopic esophagectomy versus thoracoscopic esophagectomy for local early- and intermediate-stage esophageal squamous cell carcinoma: A propensity score-matched analysis.

BACKGROUND AND OBJECTIVE: Transcervical inflatable mediastinoscopic esophagectomy (TIME) is a novel method of minimally invasive esophagectomy (MIE) for esophageal cancer. However, whether TIME is effective and feasible as conventional MIE remains unclear. This study aimed to evaluate the efficacy of TIME by comparing it with thoracoscopic esophagectomy (TE). METHODS: Surgical outcomes and relapse-free survival (RFS) rates of patients with local early- or intermediate-stage thoracic esophageal squamous cell carcinoma that underwent TIME or TE from January 2017 to December 2019 were analyzed in this retrospective study. Propensity score matching was used to control the confounding factors. RESULTS: The mean operation time in TIME was shorter than that in TE (p < 0.05). Patients in the TIME group achieved postoperative ambulation earlier than those in the TE group (p < 0.05). The rate of pulmonary complications was lower in TIME than in TE (p < 0.05). The number of lymph nodes harvested during surgery and the RFS rates of two groups did not have significant differences. CONCLUSION: TIME may be a feasible and safe method to treat local early- and intermediate-stage thoracic esophageal squamous cell carcinoma effectively and it could be a supplementary surgical method of TE for patients with poor pulmonary function or cannot undergo TE.

Comparative study on short-term efficacy of single incision plus one (SI+1) port and multiportal 3D laparoscopic minimally invasive esophagectomy.

BACKGROUND: To evaluate the safety and efficacy of single incision plus one (SI+1) port three-dimensional (3D) laparoscopic minimally invasive esophagectomy (MIE). METHODS: Clinical data of patients who underwent 3D thoracic laparoscopic MIE in our department from September 2020 to March 2021 were analyzed retrospectively. According to the different methods of laparoscopic surgery, the patients were divided into 2 groups: SI+1 port 3D laparoscopy group and multiportal 3D laparoscopy group. The operation time of the 3D laparoscopy component, amount of intraoperative blood loss, number of celiac lymph node dissections, postoperative abdominal drainage days, postoperative total abdominal drainage, postoperative complications, and length of hospital stay were analyzed. RESULTS: There was no significant difference between the 2 methods in laparoscopic operation time (30.11±5.86 vs. 28.45±4.72 min, P=0.49), intraoperative blood loss (34.44±9.82 vs. 35.91±6.25 mL, P=0.69), number of celiac lymph node dissections (8.44±3.13 vs. 7.09±2.12, P=0.27), postoperative abdominal drainage days (3.11±0.33 vs. 3.00±0.00 days, P=0.28), postoperative total abdominal drainage (95.00±23.33 vs. 92.27±11.26 mL, P=0.74), postoperative complications (22.2% vs. 27.3%, P=0.33), and hospital stay (9.67±0.71 vs. 10.18±0.87 days, P=0.17). None of the patients enrolled in the study had recurrence or death to date. CONCLUSIONS: The application of SI+1 port 3D laparoscopy in minimally invasive resection of esophageal carcinoma is safe and feasible.

E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non-small cell lung cancer.

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non-small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell-specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry-based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.

Intra-operative events and countermeasures during esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy.

BACKGROUND: Esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy as a safe and feasible minimally invasive technique has gained attention recently. But the occurrence of Intraoperative events is inevitable. It's necessary to investigate and discuss the intraoperative events and countermeasures during operation. METHODS: Intraoperative events were retrospectively reviewed in 60 patients who underwent esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy in the recent 3 years. RESULTS: There was no perioperative death and no aortic or bronchial injury. Bronchial artery injury occurred in 2 cases (3.34%), bronchial artery combined with azygos vein hemorrhage occurred in 1 case (1.67%). The pleura were injured in 3 cases (5%). Recurrent laryngeal nerve injury was noticed in 7 cases (11.67%). Thoracic duct injury occurred in 1 case (1.67%). CONCLUSIONS: As a new surgical method, esophagectomy via transcervical incision inflatable single-port mediastinoscope combined with laparoscopy is considered safe and feasible, but requires improvement when compared with traditional surgical methods. Due to the influence of surgical space and with experienced surgeons, the incidence of intraoperative events such as intraoperative bleeding and thoracic duct injury is not dominant when compared with the traditional surgical methods. Thoracic surgeons should continuously improve their clinical knowledge as well as skills. Careful preoperative examination and evaluation of the patients, being familiar with the anatomical structure and various methods, wise selection of energy devices and calmly dealing with all kinds of events are the key factors for successful surgeries with fewer intraoperative events.

Three-dimension versus two-dimension video-assisted thoracoscopic surgery for esophageal cancer: a meta-analysis.

BACKGROUND: It still remains unclear whether three-dimension (3D) video-assisted thoracoscopic surgery (VATS) for esophageal cancer is safe and reasonable. This meta-analysis aims at assessing the effectiveness and safety of 3D VATS for esophageal cancer in comparison with that of two-dimension (2D) VATS. METHODS: All the relevant data systematically analyzed in this thesis is from PubMed, Embase, The Cochrane Library, Web of Science and clinicaltrials.gov, and the time span for retrieval is from the date of the database establishment to February 2021. The research on the efficacy and safety of 3D VATS for esophageal cancer and 2D VATS is consistent with our meta-analysis. Continuous variables and dichotomy variables are compared using odds ratio, average or standard average differences with 95% confidence interval (95% CI), and P values, respectively. RESULTS: In five studies of this paper, there were 553 patients in total (3D VATS group, n=266 and 2D VATS group, n=287). Patients in the 3D group had shorter operation time [standardized mean difference (SMD) =-0.99, 95% CI: -1.66 to -0.32; P=0.004], and less bleeding (SMD =-0.88, 95% CI: -1.66 to -0.10; P=0.03) than those in the 2D group. The total amount of dissected lymph node and post-operative complications in the 2D group and the 3D group were nearly the same, showing no significant difference. DISCUSSION: The results of this meta-analysis showed that 3D VATS for esophageal cancer will be more applied and developed in the future. REGISTRATION NUMBER OF PROSPERO: CRD42021238863.

Long non-coding RNA HEIH suppresses the expression of TP53 through enhancer of zeste homolog 2 in oesophageal squamous cell carcinoma.

It is increasingly evident that the molecular and biological functions of long non-coding RNAs (lncRNA) are vital for understanding the molecular biology and progression of cancer. The lncRNA-HEIH, a newly identified lncRNA, has been demonstrated to be up-regulated in hepatocellular cancer. However, little is known about its role in oesophageal squamous cell carcinoma (ESCC). In the present study, an obvious up-regulation of lncRNA-HEIH was observed in ESCC compared to the adjacent normal tissues. Meanwhile, patients with high expression of lncRNA-HEIH have significantly poorer prognosis than those with low expression. We further found that lncRNA-HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association led to the repression of TP53. These findings indicate that lncRNA-HEIH may serve as a prognostic marker and a potential therapeutic target for ESCC.

Ubiquitination of NOTCH2 by DTX3 suppresses the proliferation and migration of human esophageal carcinoma.

The NOTCH2 gene plays a role in the development of many tumors. Deltex E3 ubiquitin ligase 3 (DTX3) was identified as a novel E3 ligase for NOTCH2 and as a potential therapeutic target for esophageal cancer. However, whether DTX3 could regulate NOTCH2 to suppress the progression of esophageal carcinoma remains unknown. In our study, NOTCH2 had higher expression in human esophageal carcinoma cell lines compared to normal human esophageal epithelial cell line, and ablation of NOTCH2 suppressed the proliferation and migration of esophageal carcinoma cells. A novel E3 ligase for NOTCH2 was identified by yeast two-hybrid (Y2H) screening, and DTX3 promoted the ubiquitination and degradation of NOTCH2. Further study showed that DTX3 overexpression suppressed the proliferation and tumorigenicity of human oesophageal carcinoma cells. The analysis of tissue samples from patients revealed that the expression of NOTCH2 was high while the expression of DTX3 was low in esophageal cancer. Furthermore, the expression of DTX3 and NOTCH2 showed a significant negative correlation in human oesophageal cancer samples. Our study suggested that the DTX3-NOTCH2 axis plays an important role in the progression of esophageal cancer, and DTX3 acts as an anti-oncogene in esophageal carcinoma, potentially offering a therapeutic target for esophageal cancer.

Magnolol inhibits growth and induces apoptosis in esophagus cancer KYSE-150 cell lines via the MAP kinase pathway.

BACKGROUND: Magnolol has shown anti-cancer activity against a variety of cancers, such as liver, breast, lung and colon cancer. However, the role of magnolol in esophagus cancer cells is unknown. METHODS: In this study, esophagus cancer cell lines including TE-1, Eca-109 and KYSE-150 were used to evaluate the cytotoxic effect of magnolol on cell proliferation, apoptosis and migration. RESULTS: We found that magnolol inhibits cellular proliferation of all three cell lines in a time- and dose-dependent manner; 20 µM magnolol markedly inhibited the migration ability of KYSE-150 cell which was accompanied with a decreased expression of MMP-2. Treatment with 100 µM magnolol significantly increased KYSE-150 cell apoptosis. We found that cleaved caspase-3, cleaved capsese-9 and Bax protein expression was increased and Bcl-2 protein expression was decreased after magnolol treatment. In addition, Magnolol had no effect on JNK but induced the phosphorylation of p38 and ERK1/2 in a concentration-dependent manner, suggesting the involvement of these kinases in the initiation of the apoptosis process. Finally, magnolol treatment significantly suppressed KYSE-150 tumor cell growth in nude mouse xenograft models. CONCLUSIONS: The results of this study provide a basis for the understanding and development of magnolol as a potential novel drug for esophagus cancer.

Shp2 Inhibits Proliferation of Esophageal Squamous Cell Cancer via Dephosphorylation of Stat3.

Shp2 (Src-homology 2 domain-containing phosphatase 2) was originally reported as an oncogene in kinds of solid tumors and hematologic malignancies. However, recent studies indicated that Shp2 may act as tumor suppressors in several tumor types. We investigated the function of Shp2 in esophageal squamous cell cancer (ESCC). The expression level of Shp2 was analyzed in tumor tissues in comparison with adjacent normal tissues of ESCC patients by immunohistochemistry and Western blot. Shp2 was knocked down by Short hairpin RNA to evaluate its function in ESCC cell lines. The relationship between Shp2 and p-Stat3 (signal transducer and activator of transcription 3) in human ESCC tissues was statistically examined. A significant low expression of Shp2 was found in ESCC tissues. Low expression of Shp2 was related to poorer overall survival in patients from The Cancer Genome Atlas (TCGA) dataset. Knockdown of Shp2 increased the growth of ESCC cell lines both in vivo and vitro. Activation of Stat3 (p-Stat3) was induced by Shp2 depletion. Expression of p-Stat3 was negatively correlated with Shp2 expression in ESCC tissues. Furthermore, knockdown of Shp2 attenuated cisplatin-sensitivity of ESCC cells. Shp2 might suppress the proliferation of ESCC by dephosphorylation of p-Stat3 and represents a novel research field for targeted therapy.

Phloretin induces apoptosis of non-small cell lung carcinoma A549 cells via JNK1/2 and p38 MAPK pathways.

Phloretin (Ph) existing in apples, pears and various vegetables is known to have antitumor activities in several cancer cell lines. However, little is known about its effect on human lung cancer cells. The aim of the present study was to see whether Ph could induce apoptosis of non-small cell lung cancer (NSCLC) cells, and explore the possible underlying mechanism of action. We found that Ph markedly induced cell apoptosis of NSCLC cell line A549, and inhibited the migration of A549 cells in a dose-dependent manner. The expression level of BAX, cleaved caspase-3 and -9, and degraded form of PARP was increased and Bcl-2 was decreased after Ph treatment. In addition, the phosphorylation of P38 MAPK, ERK1/2 and JNK1/2 was increased in a dose­dependent manner in parallel with Ph treatment. Inhibition of P38 MAPK and JNK1/2 by specific inhibitors significantly abolished the Ph-induced activation of the caspase-3 and -9. In vivo tumor-suppression assay further indicated that Ph (20 mg/kg) displayed a more significant inhibitory effect on A549 xenografts in tumor growth. All these findings indicate that Ph is able to inhibit NSCLC A549 cell growth by inducing apoptosis through P38 MAPK and JNK1/2 pathways, and therefore may prove to be an adjuvant to the treatment of NSCLC.

Reconstruction of large-size abdominal wall defect using biodegradable poly-p-dioxanone mesh: an experimental canine study.

BACKGROUND: Reconstruction of large-size abdominal wall defect (AWDs) is a huge challenge faced in current surgical practice. In this study, we aimed to evaluate the effectiveness and safety of biodegradable poly-p-dioxanone (PDO) mesh for reconstructing large-size AWDs in an experimental canine model. METHODS: Eighteen experimental canines were randomly and equally divided into three groups, namely, a PDO group, a Marlex group and a control group (n = 6 each). Following the creation of a 6 cm × 5.5 cm AWD, PDO mesh and Marlex mesh were used to reconstruct the defect in the PDO and Marlex groups, respectively. The defect was closed using relaxation sutures alone in the control group. Animals were killed 24 weeks after surgery, and reconstruction outcomes were evaluated using radiography, histology and biomechanical testing. RESULTS: All animals except those in the control group survived the experiment. The PDO group showed no wound dehiscence, herniation or infection, whereas the animals in the Marlex group exhibited marked foreign body reactions. The PDO group had less intraabdominal adhesion than the Marlex group. As shown by radiography, histology and biomechanical testing, PDO mesh exhibited complete degradation and favorable biochemical strength at 24 weeks postsurgery. CONCLUSIONS: PDO mesh implantation is an effective, safe treatment modality for reconstructing large-size AWDs.