5-Methoxytryptophan enhances the sensitivity of sorafenib on the inhibition of proliferation and metastasis for lung cancer cells.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, and effective therapies are limited. Lung cancer is a leading cause of cancer-related mortality worldwide with limited effective therapy. Sorafenib is a multi-tyrosine kinase inhibitor frequently used to treat numerous types of malignant tumors. However, it has been demonstrated that sorafenib showed moderate antitumor activity and is associated with several side effects in lung cancer, which restricted its clinical application. This study aimed to examine the antitumor effect of the combination treatment of sorafenib and 5-methoxytryptophan (5-MTP) on cell growth and metastasis of Lewis lung carcinoma (LLC) cells. METHOD: The anticancer effect of the combination treatment of sorafenib and 5-MTP was determined through cytotoxicity assay and colony forming assays. The mechanism was elucidated using flow cytometry and western blotting. Wound healing and Transwell assays were conducted to evaluate the impact of the combination treatment on migration and invasion abilities. An in vivo model was employed to analyze the effect of the combination treatment on the tumorigenic ability of LLC cells. RESULT: Our results demonstrated that the sorafenib and 5-MTP combination synergistically reduced viability and proliferation compared to sorafenib or 5-MTP treatment alone. Reduction of cyclin D1 expression was observed in the sorafenib alone or combination treatments, leading to cell cycle arrest. Furthermore, the sorafenib-5-MTP combination significantly increased the inhibitory effect on migration and invasion of LLC cells compared to the single treatments. The combination also significantly downregulated vimentin and MMP9 levels, contributing to the inhibition of metastasis. The reduction of phosphorylated Akt and STAT3 expression may further contribute to the inhibitory effect on proliferation and metastasis. In vivo, the sorafenib-5-MTP combination further reduced tumor growth and metastasis compared to the treatment of sorafenib alone. CONCLUSIONS: In conclusion, our data indicate that 5-MTP sensitizes the antitumor activity of sorafenib in LLC cells in vitro and in vivo, suggesting that sorafenib-5-MTP has the potential to serve as a therapeutic option for patients with lung cancer.

Silicon Oxy-Nitride for the Low Refractive Index Layers in the Mirror Coatings of the Cryogenic Laser Interferometer Gravitational Waves Detector.

The low refractive index layers in the mirror coatings of the room-temperature laser interferometer gravitational waves detectors are silica deposited by the ion beam sputter method. However, the silica film suffers from the cryogenic mechanical loss peak, hindering its application for the next generation detector operated at cryogenics. New low refractive index materials need to be explored. We study amorphous silicon oxy-nitride (SiON) films deposited using the method of plasma-enhanced chemical vapor deposition. By changing the N_{2}O/SiH_{4} flow rate ratio, we can tune the refractive index of the SiON smoothly from nitridelike to silicalike of ∼1.48 at 1064 nm, 1550 nm, and 1950 nm. Thermal anneal reduced the refractive index down to ∼1.46 and effectively reduced the absorption and cryogenic mechanical loss; the reductions correlated with the N─H bond concentration decrease. Extinction coefficients of the SiONs at the three wavelengths are reduced down to 5×10^{-6}∼3×10^{-7} by annealing. Cryogenic mechanical losses at 10 K and 20 K (for ET and KAGRA) of the annealed SiONs are significantly lower than the annealed ion beam sputter silica. They are comparable at 120 K (for LIGO-Voyager). Absorption from the vibrational modes of the N─H terminal-hydride structures dominates over the absorption from other terminal hydrides, the Urbach tail, and the silicon dangling bond states in SiON at the three wavelengths.

Anxiety Is a Mediator between Heart Rate Variability and Quality of Life in Chronic Obstructive Pulmonary Disease.

Autonomic nervous system (ANS) dysregulation is an important pathophysiological mechanism in patients with chronic obstructive pulmonary disease (COPD). Heart rate variability (HRV) is a common index for ANS, and HRV has been used to explore the association between ANS and clinical illnesses. This study aimed to explore the group differences in HRV, depression, anxiety, and quality of life between participants with COPD and healthy controls (HC group), and whether emotion plays a mediating role between HRV and quality of life in participants with COPD. A total of ninety-six participants with COPD and 59 participants in the HC group completed the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Saint George's Respiratory Questionnaire (SGRQ). Assessment of spirometry pulmonary function and five minute lead II electrocardiography (ECG) were also performed under the resting baseline. The COPD group had higher depression scores (F = 4.10, p = 0.008), and a lower quality of life (F = 14.44, p < 0.001) and HRV indices (such as standard deviation of RR intervals (F = 5.49, p < 0.05) and low frequency (F = 3.03, p < 0.05)) compared to the HC group. Sympathetic activation was positively correlated with depression (r = 0.312, p < 0.01), anxiety (r = 0.420, p < 0.001), and poor quality of life (r = 0.467, p < 0.001) in the COPD group. After controlling for age and sex, anxiety (ß = 0.585, p < 0.001) and sympathetic activation (ß = 0.231, p < 0.05) positively predicted poor quality of life, and lung function (ß = −0.251, p < 0.01) negatively predicted poor quality of life. Therefore, anxiety is a mediator between sympathetic activation and quality of life. Emotional and HRV screening should be applied to COPD patients in clinical practice, and emotional management or HRV biofeedback training can be used to improve anxiety and HRV for future studies.

Meta-Analysis of the Association between Asbestos Exposure and Esophageal Cancer.

BACKGROUND: We conducted a meta-analysis to quantitatively assess the association between asbestos exposure and esophageal cancer. METHODS: We systematically collected articles from three electronic databases and calculated the pooled standardized mortality rate (SMR) from the meta-analysis. Subgroup analysis according to the type of asbestos exposure, follow-up years, sample size, industry classification, sex, and high-dose exposure was conducted. RESULTS: From 242 studies, 34 cohort studies were included in our meta-analysis. Pooled SMR was positively associated with asbestos exposure and esophageal cancer (pooled SMR = 1.28; 95% confidence interval (CI) 1.19-1.38, p < 0.00001). In the subgroup analysis, (1) chrysolite, (2) four groups with follow-up over ten years, (3) the textile industry and shipyard, (4) both male and female, and (5) eight studies on highest asbestos exposure, all the subgroups showed significantly increased pooled SMRs. CONCLUSION: Asbestos exposure was significantly and positively associated with esophageal cancer, especially chrysolite. Considering the long latency period, we suggest that patients should be followed up for cancer, including esophageal cancer, for over ten years.

Siglec-E retards atherosclerosis by inhibiting CD36-mediated foam cell formation.

BACKGROUND: The accumulation of lipid-laden macrophages, foam cells, within sub-endothelial intima is a key feature of early atherosclerosis. Siglec-E, a mouse orthologue of human Siglec-9, is a sialic acid binding lectin predominantly expressed on the surface of myeloid cells to transduce inhibitory signal via recruitment of SH2-domain containing protein tyrosine phosphatase SHP-1/2 upon binding to its sialoglycan ligands. Whether Siglec-E expression on macrophages impacts foam cell formation and atherosclerosis remains to be established. METHODS: ApoE-deficient (apoE-/-) and apoE/Siglec-E-double deficient (apoE-/-/Siglec-E-/-) mice were placed on high fat diet for 3 months and their lipid profiles and severities of atherosclerosis were assessed. Modified low-density lipoprotein (LDL) uptake and foam cell formation in wild type (WT) and Siglec-E-/-- peritoneal macrophages were examined in vitro. Potential Siglec-E-interacting proteins were identified by proximity labeling in conjunction with proteomic analysis and confirmed by coimmunoprecipitation experiment. Impacts of Siglec-E expression and cell surface sialic acid status on oxidized LDL uptake and signaling involved were examined by biochemical assays. RESULTS: Here we show that genetic deletion of Siglec-E accelerated atherosclerosis without affecting lipid profile in apoE-/- mice. Siglec-E deficiency promotes foam cell formation by enhancing acetylated and oxidized LDL uptake without affecting cholesterol efflux in macrophages in vitro. By performing proximity labeling and proteomic analysis, we identified scavenger receptor CD36 as a cell surface protein interacting with Siglec-E. Further experiments performed in HEK293T cells transiently overexpressing Siglec-E and CD36 and peritoneal macrophages demonstrated that depletion of cell surface sialic acids by treatment with sialyltransferase inhibitor or sialidase did not affect interaction between Siglec-E and CD36 but retarded Siglec-E-mediated inhibition on oxidized LDL uptake. Subsequent experiments revealed that oxidized LDL induced transient Siglec-E tyrosine phosphorylation and recruitment of SHP-1 phosphatase in macrophages. VAV, a downstream effector implicated in CD36-mediated oxidized LDL uptake, was shown to interact with SHP-1 following oxidized LDL treatment. Moreover, oxidized LDL-induced VAV phosphorylation was substantially lower in WT macrophages comparing to Siglec-E-/- counterparts. CONCLUSIONS: These data support the protective role of Siglec-E in atherosclerosis. Mechanistically, Siglec-E interacts with CD36 to suppress downstream VAV signaling involved in modified LDL uptake.

Galectin-1 Restricts Vascular Smooth Muscle Cell Motility Via Modulating Adhesion Force and Focal Adhesion Dynamics.

Vascular smooth muscle cell (VSMC) migration play a key role in the development of intimal hyperplasia and atherosclerosis. Galectin-1 (Gal-1) is a redox-sensitive ß-galactoside-binding lectin expressed in VSMCs with intracellular and extracellular localizations. Here we show that VSMCs deficient in Gal-1 (Gal-1-KO) exhibited greater motility than wild type (WT) cells. Likewise, Gal-1-KO-VSMC migration was inhibited by a redox-insensitive but activity-preserved Gal-1 (CSGal-1) in a glycan-dependent manner. Gal-1-KO-VSMCs adhered slower than WT cells on fibronectin. Cell spreading and focal adhesion (FA) formation examined by phalloidin and vinculin staining were less in Gal-1-KO-VSMCs. Concomitantly, FA kinase (FAK) phosphorylation was induced to a lower extent in Gal-1-KO cells. Analysis of FA dynamics by nocodazole washout assay demonstrated that FA disassembly, correlated with FAK de-phosphorylation, was faster in Gal-1-KO-VSMCs. Surface plasmon resonance assay demonstrated that CSGal-1 interacted with α5ß1integrin and fibronectin in a glycan-dependent manner. Chemical crosslinking experiment and atomic force microscopy further revealed the involvement of extracellular Gal-1 in strengthening VSMC-fibronectin interaction. In vivo experiment showed that carotid ligation-induced neointimal hyperplasia was more severe in Gal-1-KO mice than WT counterparts. Collectively, these data disclose that Gal-1 restricts VSMC migration by modulating cell-matrix interaction and focal adhesion turnover, which limits neointimal formation post vascular injury.

Enteral nutrition and quality of life in patients undergoing chemoradiotherapy for esophageal carcinoma: a comparison of nasogastric tube, esophageal stent, and ostomy tube feeding.

BACKGROUND AND AIMS: This study prospectively recruited esophageal squamous cell carcinoma patients who received esophageal stent, nasogastric tube (NGT), or jejunostomy/gastrostomy feeding to compare the changes in nutritional status and quality of life during chemoradiation therapy (CRT). METHODS: In total, 81 patients were analyzed (stent, 7; surgical ostomy, 26; NGT, 19; oral intake, 29). An NGT was inserted when, despite medication, dysphagia or pain worsened with oral feeding during CRT. Serial body weight and daily narcotic demand were recorded. Changes in serum albumin level and quality of life were also assessed. In subgroup analysis comparing NGT and prophylactic surgical ostomy feeding, 5 patients with total occlusion in the ostomy group were excluded. RESULTS: Patients in all groups had similar decreases in mean body weight with an overall change of -6.41% ± 5.21% at the end of CRT. The stent group had significantly worse pain, decreased albumin (-1.03 ± .9 mg/dL), and decreased quality of life across CRT compared with the other groups. In subgroup analysis the stent group had significantly higher weight loss, whereas the NGT group had higher narcotic demand and slightly worse quality of life. Two patients (7.7%) had ileus days after jejunostomy creation. Five patients (23.8%) among those received prophylactic ostomy creation and scarcely used it. CONCLUSIONS: These preliminary results raise concerns that use of esophageal stents may be less suitable in patients undergoing CRT. Tube feeding by means of transnasal or percutaneous routes appear to be comparably effective during CRT, but both have advantages and disadvantages. We suggest a careful endoscopic evaluation to select the population more appropriate for NGT feeding on an as-needed basis during CRT.

Expedite recovery from esophagectomy and reconstruction for esophageal squamous cell carcinoma after perioperative management protocol reinvention.

BACKGROUND: Surgery for esophageal cancer is invasive and challenging, and always to be followed with arduous post-operative care and recovery. This study, maybe one of the first in Asian populations, is to determine whether a reinvented protocol for perioperative management for esophageal cancer surgery which is being implemented in our department, will lead to a faster convalescence and also significantly decrease financial burdens garnered by patients during hospitalization. METHODS: Operated on by the same surgeon and team in the same hospital, consecutive patients who had received esophagectomy and reconstruction for esophageal squamous cell carcinoma were retrospectively reviewed. On the basis of two different treatment periods, patients were divided into two groups: A and B. Group A was patients who had received the new reinvented protocol between 2012 and 2016, while group B patients were those having received the previous protocol between 2008 and 2011. Their demographics, post-operative outcome, and hospital charges were collected and compared. RESULTS: There were 64 patients in group A, and 69 in group B. Ventilator days (P<0.001), ICU stay (P<0.001), and post-operative stay (P<0.001) were significantly shorter in group A patients. Complication rates were similar between the two groups. No hospital mortality was noted in either group. Hospital charges in group A were found to be perceptively lower, although not statistically significant (P value =0.078). CONCLUSIONS: The current protocol of perioperative care effectively ameliorated convalescence after esophagectomy and reconstruction for esophageal squamous cell carcinoma without increasing complication rate or mortality. It is also potentially more practical in future health care policies during this era of financial shortage.

Glove-Finger Extraction Technique in Uniportal Video-Assisted Thoracoscopic Surgery.

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (VATS) is increasingly being performed worldwide. During the operation, specimen extraction from a small incision less than or equal to 2 cm can be challenging without the use of a commercial specimen retrieval device. There have been no reports regarding the use of the glove-finger technique in uniportal VATS. The aim of this study was to assess the feasibility of the alternative specimen retrieval method by glove-finger technique. METHODS: We retrospectively investigated 50 patients with peripheral lung lesions who underwent uniportal VATS wedge resection with a 2-cm incision at Kaohsiung Medical University Hospital between August 2015 and December 2016. The cut end of the glove-finger was used to extract the specimen. RESULTS: Fifty-five wedge-resected specimens were extracted successfully by glove-finger technique. There was no conversion to two-port nor three-port VATS. After intraoperative frozen section analysis for all specimens, 24 were revealed to have primary lung cancer and subsequently underwent completion lobectomy or segmentectomy; the other 31 showed 10 pulmonary metastases, 9 pulmonary benign lesions, and 12 pulmonary infectious lesions. All specimens were resected with free margins and the mean diameter of the lesions was 1.64 ± 0.59 cm (range: 0.2-2.6 cm) by pathological examination. No intraoperative complication related to the technique was observed. CONCLUSIONS: This is the first study to reveal the efficacy and benefits of the glove-finger extraction technique in uniportal VATS. In our preliminary experience, this method can decrease costs without compromising the quality and safety of patient care.

Video-assisted thoracoscopic surgery for postoperative recurrent primary spontaneous pneumothorax.

OBJECTIVES: Postoperative recurrent primary spontaneous pneumothorax (PSP) is a troublesome complication and an important issue to be discussed. This study is to determine whether Re-video assisted thoracoscopic surgery (VATS) should be performed for postoperative recurrent PSP (PORP). MATERIALS AND METHODS: Patients who had underwent needlescopic VATS for PSP between Jan. 2007 and Dec. 2011 were reviewed. RESULTS: VATS was initially performed on 239 patients with PSP in total. Eleven patients were found to have PORP during a follow-up period of 36.95 months. Nine patients received Re-VATS and only two patients receiving conservative treatment had no further recurrence. No conversion to thoracotomy, blood transfusion and prolong air leak were recorded. CONCLUSIONS: Even for smaller size cases, Re-VATS, which is technically feasible, safe and effective with better cosmetics and minor postoperative pain, should be a strong contender as priority treatment.