Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor.

Macrophages form a major cell population in the tumor microenvironment. They can be activated and polarized into tumor-associated macrophages (TAM) by the tumor-derived soluble molecules to promote tumor progression and metastasis. Here, we used comparative metabolomics coupled with biochemical and animal studies to show that cancer cells release succinate into their microenvironment and activate succinate receptor (SUCNR1) signaling to polarize macrophages into TAM. Furthermore, the results from in vitro and in vivo studies revealed that succinate promotes not only cancer cell migration and invasion but also cancer metastasis. These effects are mediated by SUCNR1-triggered PI3K-hypoxia-inducible factor 1α (HIF-1α) axis. Compared with healthy subjects and tumor-free lung tissues, serum succinate levels and lung cancer SUCNR1 expression were elevated in lung cancer patients, suggesting an important clinical relevance. Collectively, our findings indicate that the secreted tumor-derived succinate belongs to a novel class of cancer progression factors, controlling TAM polarization and promoting tumorigenic signaling.

Therapeutic impact of epidermal growth factor receptor tyrosine kinase inhibitor with various treatment combinations for advanced lung adenocarcinoma.

OBJECTIVES: Tyrosine kinase inhibitors (TKIs) are the primary therapeutic option for patients with advanced-stage epidermal growth factor receptor-mutant (EGFR-m) lung adenocarcinoma. However, the role of EGFR-TKIs in advanced-stage lung cancer is uncertain regardless of therapeutic methods. This study investigated the outcome of the impact of epidermal growth factor receptor (EGFR)-TKI in patients with advanced lung adenocarcinoma treated with various therapeutic strategies. METHODS: This retrospective analysis used cancer registry data from 1159 patients with lung cancer treated between January 2015 and December 2017 at Tri-Service General Hospital. Only patients with lung adenocarcinoma stages 3B and four were selected for the study. All lung adenocarcinoma patients with ever TKI treatment had an EGFR mutation. RESULTS: Three-hundred sixty-two patients with advanced lung adenocarcinoma with complete medical records were enrolled. According to personalized therapeutic processes, they were divided into nine groups: only TKI treatment, only chemotherapy (CT), TKI with lung cancer salvage surgery, TKI with CT, TKI with radiotherapy (RT), CT with lung cancer salvage surgery, CT with RT, TKI with CT, and lung cancer salvage surgery. A multivariate Cox regression analysis showed TKI with lung cancer salvage surgery (HR: 4.675, p = 0.005) is the only good prognostic treatment. The poor predictors for overall survival were only CT (HR: 0.336, p = 0.048) and TKI with CT (HR: 0.359, p = 0.023). Kaplan-Meier survival analysis showed a statistical significance in an average overall survival (OS) of ever TKI treatment and never TKI treatment (33.24 vs. 17.64 months, p < 0.001). Furthermore, TKI usage duration was statistically increased in TKI with lung cancer salvage surgery (40.4 ± 20.7 vs 14.96 ± 13.13 months, p < 0.001). The survival rate (p = 0.033) and OS (p < 0.001) in lung cancer salvage surgery were statistically better than the group of TKI without surgery. CONCLUSION: The best therapeutic strategy for advanced lung adenocarcinoma is TKI with lung cancer salvage surgery, according to significantly longer OS and better survival. It also prolonged TKI usage. Mutated EGFR lung adenocarcinoma patients with ever TKI treatment had significantly better survival than with other treatments. Regardless of the combination of other treatments, EGFR mutation with TKI therapy is recommended as a positive prognostic factor for patients with lung adenocarcinoma.

Using machine learning to determine the correlation between physiological and environmental parameters and the induction of acute mountain sickness.

BACKGROUND: Recent studies on acute mountain sickness (AMS) have used fixed-location and fixed-time measurements of environmental and physiological variable to determine the influence of AMS-associated factors in the human body. This study aims to measure, in real time, environmental conditions and physiological variables of participants in high-altitude regions to develop an AMS risk evaluation model to forecast prospective development of AMS so its onset can be prevented. RESULTS: Thirty-two participants were recruited, namely 25 men and 7 women, and they hiked from Cuifeng Mountain Forest Park parking lot (altitude: 2300 m) to Wuling (altitude: 3275 m). Regression and classification machine learning analyses were performed on physiological and environmental data, and Lake Louise Acute Mountain Sickness Scores (LLS) to establish an algorithm for AMS risk analysis. The individual R2 coefficients of determination between the LLS and the measured altitude, ambient temperature, atmospheric pressure, relative humidity, climbing speed, heart rate, blood oxygen saturation (SpO2), heart rate variability (HRV), were 0.1, 0.23, 0, 0.24, 0, 0.24, 0.27, and 0.35 respectively; incorporating all aforementioned variables, the R2 coefficient is 0.62. The bagged trees classifier achieved favorable classification results, yielding a model sensitivity, specificity, accuracy, and area under receiver operating characteristic curve of 0.999, 0.994, 0.998, and 1, respectively. CONCLUSION: The experiment results indicate the use of machine learning multivariate analysis have higher AMS prediction accuracies than analyses utilizing single varieties. The developed AMS evaluation model can serve as a reference for the future development of wearable devices capable of providing timely warnings of AMS risks to hikers.

Prognostic factors associated with 18FDG-PET/CT in esophageal squamous cell carcinoma after trimodality treatment.

PURPOSE: This study aimed to determine the pathological complete response (pCR), overall survival (OS), and disease-free survival (DFS) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) using post-neoadjuvant chemoradiotherapy (nCRT) F-18-fluorodeoxyglucose (18FDG). METHODS: This is a retrospective study of patients with locally advanced ESCC receiving nCRT and then esophagectomy between January 2011 and December 2018 in the Tri-Service General Hospital, Taipei, Taiwan. A total of 50 patients were enrolled in the study. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model. Univariate and multivariate analysis were used to determine the independent prognostic factors. RESULTS: Fifty patients were enrolled in the study, and 18 had pathological complete response. Post-nCRT SUVmax ≥ 3 is a poor prognostic factor associated with overall survival (HR: 3.665, P = 0.013) and disease-free survival (HR: 3.417, P = 0.011). Poor prognosis was found in the non-pCR plus post-nCRT SUVmax ≥ 3 group compared with pCR plus post-nCRT SUVmax < 3 group. CONCLUSIONS: SUVmax ≥ 3 is a poor prognostic factor in esophageal squamous cell carcinoma after trimodality treatment, even in patients having pathological complete response.

Intrapericardial Thymoma Presented as Pericardial Tamponade with Post-Operative Myasthenia Gravis.

BACKGROUND: Thymoma is an epithelial mass arising from the thymus. Most thymomas are located in the anterior mediastinum. Ectopic intrapericardial thymoma is very unusual; to date, only eight cases of pericardial thymoma have been reported. Among thymoma patients, 20% to 25% are associated with myasthenia gravis. However, postoperative myasthenia gravis occurs in less than 1% of cases. Here, we share a rare case of ectopic intrapericardial thymoma that developed postoperative myasthenia gravis six months after surgery. CASE PRESENTATION: A 66-year-old woman visited the outpatient department due to productive cough and chest pain. Chest radiography showed increased soft tissue opacity over the mediastinum. A soft tissue mass in the pericardium and a ground glass nodule in right upper lung were noted using chest computed tomography. The diagnosis of thymoma, type B2, pT3N0M0, and stage IIIA and synchronous adenocarcinoma in situ of the right upper lung was confirmed after surgical removal. Six months later, the patient developed postoperative myasthenia gravis. CONCLUSIONS: Thymoma is rarely considered a differential diagnosis in pericardial tumors. Surgical removal with adjuvant radiation therapy should be performed considering the malignancy potential of thymomas and cardiac complications. In patients without myasthenia gravis, a small chance of postoperative myasthenia gravis remains. Patients should be carefully monitored for myasthenia gravis after surgery.

Simultaneous Patent Blue Dye Injections Aid in the Preoperative CT-Guided Localization of Multiple Pulmonary Nodules.

Background and Objectives: Clinically, a major challenge of multiple nodule localization is puncture-related pneumothorax, which may hamper the successful localization. This study aims to investigate and compare the efficacy and safety of the simultaneous and sequential patent blue dye (PBD) injections for identifying multiple pulmonary nodules during preoperative CT-guided localization. Materials and Methods: Sixty-one consecutive patients with multiple pulmonary nodules who underwent preoperative CT-guided localization with PBD injections between January 2020 and December 2020 were retrospectively enrolled. Of these patients, 31 patients with 64 nodules who underwent simultaneous injections were designated as the simultaneous group; the remaining 30 patients with 63 nodules who underwent sequential punctures were designated as the sequential group. The clinical and radiological features, technical information, pathological results, and procedure-related variables and complications of the two groups were reviewed and analyzed. Results: The localization success rate of the simultaneous group was higher than that of the sequential group (100% [64/64] vs. 93.7% [59/63], p = 0.041). The incidences of pneumothorax (32.3 vs. 33.3%, p = 0.929) and pulmonary hemorrhage (6.3 vs. 3.0%, p = 1) were not significantly different between the two groups, and all cases were minor, which did not require further intervention. Additionally, a significantly lower radiation dose (2.7 vs. 3.5 mSv, p = 0.001) and a shorter procedure time (20.95 vs. 25.28 min, p = 0.001) were observed in the simultaneous group than in the sequential group. Conclusions: Compared with the sequential method, simultaneous PBD injections may improve the localization success rate with a shorter procedure time and less radiation exposure if the patient with multiple pulmonary nodules can be approached in a single position. Further prospective studies are needed to validate these results.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Differentiating focal interstitial fibrosis from adenocarcinoma in persistent pulmonary subsolid nodules (> 5 mm and < 20 mm): the role of coronal thin-section CT images.

OBJECTIVES: To investigate thin-section computed tomography (CT) features of pulmonary subsolid nodules (SSNs) with sizes between 5 and 20 mm to determine predictive factors for differentiating focal interstitial fibrosis (FIF) from adenocarcinoma. METHODS: From January 2017 to December 2018, 169 patients who had persistent SSNs 5-20 mm in size and underwent preoperative nodule localization were enrolled. Patient characteristics and thin-section CT features of the SSNs were reviewed and compared between the FIF and adenocarcinoma groups. Univariable and multivariable analyses were used to identify predictive factors of malignancy. Receiver operating characteristic (ROC) curve analysis was used to quantify the performance of these factors. RESULTS: Among the 169 enrolled SSNs, 103 nodules (60.9%) presented as pure ground-glass opacities (GGOs), and 40 (23.7%) were FIFs. Between the FIF and adenocarcinoma groups, there were significant differences (p< 0.05) in nodule border, shape, thickness, and coronal/axial (C/A) ratio. Multivariable analysis demonstrated that a well-defined border, a nodule thickness >4.2, and a C/A ratio >0.62 were significant independent predictors of malignancy. The performance of a model that incorporated these three predictors in discriminating FIF from adenocarcinoma achieved a high area under the ROC curve (AUC, 0.979) and specificity (97.5%). CONCLUSIONS: For evaluating persistent SSNs 5-20 mm in size, the combination of a well-defined border, a nodule thickness > 4.2, and a C/A ratio > 0.62 is strongly correlated with malignancy. High accuracy and specificity can be achieved by using this predictive model. KEY POINTS: • Thin-section coronal images play an important role in differentiating FIF from adenocarcinoma. • The combination of a well-defined border, nodule thickness>4.2 mm, and C/A ratio >0.62 is associated with malignancy. • This predictive model may be helpful for managing persistent SSNs between 5 and 20 mm in size.

Prognostic value of positron emission tomography in resected stage IA non-small cell lung cancer.

OBJECTIVES: To investigate the role of PET in predicting the prognosis of resected stage IA non-small cell lung cancer (NSCLC) and planning individualized therapeutic strategies. METHODS: We retrospectively reviewed the data of patients who underwent surgical resection for lung cancer between January 2004 and December 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. RESULTS: We evaluated 998 cases; 637 patients with pathological stage I disease were categorized as follows: stage IA1 (251 cases), stage IA2 (250 cases), and stage IA3 (136 cases). The mean follow-up period was 109 months. Significant differences were observed in sex, tumor differentiation, epidermal growth factor receptor mutation, smoking habits, lymphovascular space invasion, tumor size, maximum standard uptake value (SUVmax), and carcinoembryonic antigen level among the groups. Multivariable Cox regression revealed that ground-glass opacity ratio (hazard ratio (HR) = 0.001) and tumor SUVmax independently predicted the postoperative risk of relapse for stage IA3 NSCLC. The HR for SUVmax > 4 was 8.986 (p < 0.001). The 5-year overall survival (OS) rates were 87.2%, 92.9%, and 82.7%, and the 5-year disease-free survival (DFS) rates were 93.2%, 84.2%, and 70.51% for stage IA1, IA2, and IA3 NSCLC, respectively (both p < 0.001). OS and DFS rates were poor in stage IA3 NSCLC patients with an SUVmax uptake > 4 (OS, 71.0% and 92.2%; DFS, 50.2% and 87.3%, for SUVmax > 4 and ≤ 4, respectively; both p = 0.001). CONCLUSIONS: SUVmax was a prognostic factor for resected stage IA NSCLC. Postoperative treatment may be considered for IA3 NSCLC with SUVmax > 4. KEY POINTS: • PET helps surgeons to assess patients with early-stage lung cancer. • This retrospective study revealed that PET plays an influential role in predicting the prognosis of resected lung cancer. • Better prognostication aids better planning of therapeutic strategies with diversification.

Severity of Pectus Excavatum is a Risk Factor for Primary Spontaneous Pneumothorax.

BACKGROUND AND OBJECTIVE: This study aimed to investigate the relationship between bleb formation, primary spontaneous pneumothorax (PSP) and pectus excavatum (PE). METHODS: From July 2005 to December 2016, the records of 514 patients with PE who underwent the Nuss procedure were obtained from a prospectively collected database and reviewed. Clinical features, images and treatments were analyzed retrospectively. RESULTS: The incidence rate of bleb formation was 26.5% in PE patients. The bleb group had a greater body height (174.4 cm vs. 170.4 cm, p < 0.001), a higher Haller index (HI; 4.2 vs. 3.43, p < 0.001) and a higher risk of developing PSP than the non-bleb group (risk ratio 9.8, p = 0.002). HI values larger than 3.615 had good discriminatory power for predicting bleb formation in patients with PE. With each increase in the HI, PE patients had a 2.2-fold greater odds ratio of bleb formation (odds ratio 2.221, CI 1.481-3.330, p < 0.001). CONCLUSION: We discovered that a high percentage of PE patients have bleb formation and a higher risk of PSP, especially those with an HI >3.615. High-resolution computed tomography of the chest may be useful for evaluating both the HI and the presence of blebs in the lungs before performing a corrective surgical procedure.

Bidirectional association between tuberculosis and sarcoidosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) and sarcoidosis are both granulomatous diseases with potential interassociations. However, much uncertainty remains; thus, the present study aimed to clarify the association between these diseases. METHODS: We established two cohorts in this retrospective longitudinal cohort study using data obtained from the Taiwan National Health Insurance Database from 2000 to 2015. One cohort, which comprised 31 221 patients with TB and 62 442 age-, sex- and index year-matched controls, was used to analyse the risk of sarcoidosis; the other cohort comprised 2442 patients with sarcoidosis and 9688 controls and was used to assess the risk of TB. A Cox proportional hazards model adjusted for potential confounders was used in each cohort. RESULTS: Patients with TB showed an 8.09-fold higher risk of developing sarcoidosis than non-TB subjects (95% CI = 3.66-17.90), whereas patients with sarcoidosis showed a 1.85-fold higher risk of developing TB than non-sarcoidosis subjects (95% CI = 1.36-2.50). The TB subtype analysis revealed the highest risk of developing sarcoidosis in patients with extrapulmonary TB, and the highest risk of developing extrapulmonary TB was observed in patients with sarcoidosis compared with non-sarcoidosis subjects. Patients with TB showed a higher risk of developing sarcoidosis throughout the follow-up period, but patients with sarcoidosis only showed a higher risk of developing TB within the first year. CONCLUSION: TB is a risk factor for developing sarcoidosis. The results of this bidirectional cohort study also highlight the clinical difficulty of diagnosing sarcoidosis and TB.

Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells.

Cisplatin is still the primary therapeutic choice for advanced lung cancers without driver mutations. The occurrence of cisplatin resistance is a major clinical problem in lung cancer treatment. The natural extracted agent emetine reportedly has anticancer effects. This study aimed to explore the possible role of emetine in cisplatin resistance. We used cell viability, Western blot, and Wnt reporter assays to show that emetine suppresses proliferation, ß-catenin expression, and Wnt/ß-catenin signaling in non-small cell lung cancer (NSCLC). The synergism of emetine and cisplatin was assessed by constructing isobolograms and calculating combination index (CI) values using the Chou-Talalay method. Emetine effectively synergized with cisplatin to suppress the proliferation of cancer cells. Furthermore, nuclear ß-catenin and cancer stem cell-related markers were upregulated in the cisplatin-resistant subpopulation of CL1-0 cells. Emetine enhanced the anticancer efficacy of cisplatin and synergized with cisplatin in the cisplatin-resistant subpopulation of CL1-0 cells. Taken together, these data suggest that emetine could suppress the growth of NSCLC cells through the Wnt/ß-catenin pathway and contribute to a synergistic effect in combination with cisplatin.

Prognostic potential of initial CT changes for progression-free survival in gefitinib-treated patients with advanced adenocarcinoma of the lung: a preliminary analysis.

OBJECTIVES: We aimed to determine whether initial tumour responses measured during short-term follow-up computed tomography (CT) examinations after baseline examinations would correlate with clinical outcomes in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR)-targeted therapy. METHODS: A total of 86 gefitinib-treated patients with advanced adenocarcinoma of the lung were retrospectively reviewed. All patients underwent baseline and short-term follow-up CT examinations. The new response criteria (NRC) by Lee et al. were used for the response evaluations. A Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses were used to evaluate correlations between the initial tumour changes and progression-free and overall survival (PFS, OS). RESULTS: Better separation and smaller p values were observed for both PFS and OS when good and poor disease responses (as defined by NRC) were compared after excluding tumours with characteristic morphologies. Early tumour changes correlated with PFS in a size-dependent manner. Moreover, a stronger association was observed between size changes and PFS when characteristic morphology was also considered. CONCLUSIONS: Initial changes in tumour size during short-term post-treatment CT examinations could act as a potential prognostic imaging surrogate for PFS in gefitinib-treated patients with advanced adenocarcinoma of the lung. KEY POINTS: • Initial responses to gefitinib on computed tomography significantly correlate with clinical outcomes. • Regardless of morphology, size decrease greater than 30 % predicts prolonged progression-free and overall survival. • Combination of size and morphological changes yields prognostic independence regarding progression-free survival.

Localization of nonpalpable pulmonary nodules using CT-guided needle puncture.

BACKGROUND: Surgical resection of small pulmonary nodule is challenging via thoracoscopic procedure. We describe our experience of computed tomography (CT)-guided needle puncture localization of indeterminate pulmonary nodules prior to video-assisted thoracoscopic surgery (VATS). METHODS: From January 2011 to July 2014, 78 consecutive patients underwent CT-guided marking for the localization of 91 small pulmonary nodules. We retrospectively reviewed the clinical data, technical details, surgical findings and pathologic results, and complications associated with CT-guided localization. RESULTS: Seventy-eight consecutive patients (36 men and 42 women) underwent CT-guided marking localization of 91 indeterminate pulmonary nodules (62 pure ground-glass opacity nodules, 27 part-solid nodules, and 2 solid nodules). The mean size of the nodules was 8.6 mm (3.0-23.0 mm). The mean pleural distance between the nodule and lung surface was 11.5 mm (3.0-31.3 mm). The mean procedure time of CT-guided localization was 15.2 min (8-42 min). All patients stood the procedures well without requiring conversion to open thoracotomy. Twenty-four patients (30.77%) developed pneumothorax after the procedures. Only one patient required retention of the puncture needle introducer for air drainage. The mean visual assessment pain score was 1.7 (0-3). Fifty-seven nodules (62.63%) were confirmed as malignances, including 45 primary lung cancer, and 34 nodules (37.37%) were confirmed as benign lesions. CONCLUSIONS: CT-guided needle puncture can be an effective and safe procedure prior to VATS, enabling accurate resection and diagnosis of small pulmonary nodules.

Value of ¹8F-FDG uptake on PET/CT and CEA level to predict epidermal growth factor receptor mutations in pulmonary adenocarcinoma.

PURPOSE: The identification of the mutation status of the epidermal growth factor receptor (EGFR) is important for the optimization of treatment in patients with pulmonary adenocarcinoma. The acquisition of adequate tissues for EGFR mutational analysis is sometimes not feasible, especially in advanced-stage patients. The aim of this study was to predict EGFR mutation status in patients with pulmonary adenocarcinoma based on (18)F-fluorodeoxyglucose (FDG) uptake and imaging features in positron emission tomography/computed tomography (PET/CT), as well as on the serum carcinoembryonic antigen (CEA) level. METHODS: We retrospectively reviewed 132 pulmonary adenocarcinoma patients who underwent EGFR mutation testing, pretreatment FDG PET/CT and serum CEA analysis. The associations between EGFR mutations and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, serum CEA level and CT imaging features were analyzed. Receiver-operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors. RESULTS: EGFR mutations were identified in 69 patients (52.2 %). Patients with SUVmax ≥6 (p = 0.002) and CEA level ≥5 (p = 0.013) were more likely to have EGFR mutations. The CT characteristics of larger tumors (≥3 cm) (p = 0.023) and tumors with a nonspiculated margin (p = 0.026) were also associated with EGFR mutations. Multivariate analysis showed that higher SUVmax and CEA level, never smoking and a nonspiculated tumor margin were the most significant predictors of EGFR mutation. The combined use of these four criteria yielded a higher area under the ROC curve (0.82), suggesting a good discrimination. CONCLUSION: The combined evaluation of FDG uptake, CEA level, smoking status and tumor margins may be helpful in predicting EGFR mutation status in patients with pulmonary adenocarcinoma, especially when the tumor sample is inadequate for genetic analysis or genetic testing is not available. Further large-scale prospective studies are needed to validate these results.

Risk factors of postoperative recurrences in patients with clinical stage I NSCLC.

BACKGROUND: Despite advances in radiation therapy, chemotherapy, and newly developed molecular targeting therapies, long-term survival after resection for patients with NSCLC remains less than 50%. We investigated factors predicting postoperative locoregional recurrences and distant metastases in patients with clinical stage I non-small-cell lung cancer (NSCLC) after surgical resection. METHODS: All patients with clinical stage I NSCLC, who underwent surgical resection between January 2002 and June 2006, were reviewed retrospectively. Multiple logistic regression analyses were used to identify independent risk factors for patients with locoregional recurrences and distant metastases. RESULTS: A total of 261 patients were eligible. Overall survival was significant related to locoregional recurrences (P = 0.03) and distant metastases (P <0.001). There were significant differences of locoregional recurrence in tumor differentiation (P = 0.032) and advanced pathological stage (P = 0.002). In the group of distant metastases, there were significant differences in tumor differentiation (P = 0.035), lymphovascular space invasion (P = 0.031). Among the relationship between pattern of distant metastasis and clinicopathologic variables in patients with clinical stage I NSCLC, SUVmax (P = 0.02) and tumor size (P = 0.001) had significant differences. According to multiple logistic regression analysis, tumor differentiation is the only risk factor of postoperative outcome for locoregional recurrence and serum CEA (>3.5 ng/mL) is the predictor of distant metastasis. CONCLUSIONS: Tumor differentiation and serum CEA were predictors of postoperative relapse for clinical stage I NSCLC after surgical resection. Risk factors of postoperative recurrence in patients with clinical stage I NSCLC may enable us to optimize the patient selection for postoperative adjuvant therapies or neoadjuvant treatment before surgery.

Nuclear translocation of Axl contributes to the malignancy of oral cancer cells.

Background/purpose: Dysregulation of receptor tyrosine kinases is implicated in cancer development. This study aimed to investigate the nuclear translocation of Axl, a membrane protein and receptor tyrosine kinase in cancer malignancy. Materials and methods: We examined Axl's entry into the cell nucleus and validated it with the nuclear export inhibitor leptomycin. Transfection experiments with mutated nuclear localization signals were conducted to assess the impact of reduced nuclear Axl levels on cancer cell malignancy. Additionally, we evaluated the effects of decreased nuclear Axl on sensitivity to radiation and cisplatin, a chemotherapeutic drug. Results: In the present study, we observed nuclear translocation of Axl in cancer cells. Reducing nuclear Axl levels led to a decrease in cancer cell malignancy. This nuclear translocation was further validated using a nuclear export inhibitor, leptomycin. Additionally, transfection experiments with mutated nuclear localization signals confirmed the functional significance of Axl's nuclear localization. Notably, decreased nuclear Axl levels also increased the sensitivity of cancer cells to radiation and cisplatin treatment. Conclusion: This study suggests that Axl's nuclear translocation plays a significant role in cancer malignancy. Targeting Axl's nuclear localization could offer a potential strategy to inhibit cancer progression and improve the efficacy of radiation and chemotherapy treatments.

MiR-34a functions as a tumor suppressor in oral cancer through the inhibition of the Axl/Akt/GSK-3ß pathway.

Background/purpose: Oral cancer is a prevalent malignancy affecting men globally. This study aimed to investigate the regulatory role of miR-34a in oral cancer cells through the Axl/Akt/glycogen synthase kinase-3ß (GSK-3ß) pathway and its impact on cellular malignancy. Materials and methods: We examined the effects of miR-34a overexpression on the malignancy of oral cancer cells. Multiple oral cancer cell lines were assessed to determine the correlation between endogenous miR-34a and Axl levels. Transfection experiments with miR-34a were conducted to analyze its influence on Axl mRNA and protein expression. Luciferase reporter assays were performed to investigate miR-34a's modulation of Axl gene transcription. Manipulation of miR-34a expression was utilized to demonstrate its regulatory effects on oral cancer cells through the Axl/Akt/GSK-3ß pathway. Results: Overexpression of miR-34a significantly suppressed the malignancy of oral cancer cells. We observed an inverse correlation between endogenous miR-34a and Axl levels across multiple oral cancer cell lines. Transfection of miR-34a resulted in decreased Axl mRNA and protein expression, and luciferase reporter assays confirmed miR-34a-mediated modulation of Axl gene transcription. The study revealed regulatory effects of miR-34a on oral cancer cells through the Axl/Akt/GSK-3ß pathway, leading to alterations in downstream target genes involved in cellular proliferation and tumorigenesis. Conclusion: Our findings highlight the significance of the miR-34a/Axl/Akt/GSK-3ß signaling axis in modulating the malignancy of oral cancer cells. Targeting miR-34a may hold therapeutic potential in oral cancer treatment, as manipulating its expression can attenuate the aggressive behavior of oral cancer cells via the Axl/Akt/GSK-3ß pathway.

The application of electrical impedance tomography and surgical outcomes of thoracoscope-assisted surgical stabilization of rib fractures in severe chest trauma.

Serious blunt chest trauma usually induces hemothorax, pneumothorax, and rib fractures. More studies have claimed that early video-assisted thoracoscopic surgery with surgical stabilization of rib fractures (SSRF) results in a good prognosis in patients with major trauma. This study aimed to verify the outcomes in patients with chest trauma whether SSRF was performed. Consecutive patients who were treated in a medical center in Taiwan, for traumatic events between January 2015 and June 2020, were retrospectively reviewed. This study focused on patients with major trauma and thoracic injuries, and they were divided into groups based on whether they received SSRF. We used electrical impedance tomography (EIT) to evaluate the change of ventilation conditions. Different scores used for the evaluation of trauma severity were also compared in this study. Among the 8396 patients who were included, 1529 (18.21%) had major trauma with injury severity score > 16 and were admitted to the intensive care unit initially. A total of 596 patients with chest trauma were admitted, of whom 519 (87%) survived. Younger age and a lower trauma score (including injury severity scale, new injury severity score, trauma and injury severity score, and revised trauma score) account for better survival rates. Moreover, 74 patients received SSRF. They had a shorter intensive care unit (ICU) stay (5.24, p = 0.045) and better performance in electrical impedance tomography (23.46, p < 0.001). In patients with major thoracic injury, older age and higher injury survival scale account for higher mortality rate. Effective surgical stabilization of rib fractures shortened the ICU stay and helped achieve better performance in EIT. Thoracoscope-assisted rib fixation is suggested in severe trauma cases.