LINC00365 inhibited lung adenocarcinoma progression and glycolysis via sponging miR-429/KCTD12 axis.

This study researched the function of long non-coding RNA LINC00365 in lung adenocarcinoma (LAD) progression. LINC00365, miR-429, and KCTD12 expression in the LAD clinical tissues and cells were detcetd by qRT-PCR and Western blot. LINC00365, miR-429, and KCTD12 effects on H1975 cells malignant phenotype were detected by cell counting kit-8 assay, clone formation experiment, Transwell experiment, and glycolysis. Dual luciferase reporter gene assay and RNA pull-down assay were implemented. LINC00365 effect on H1975 cells in vivo growth was detected. LINC00365 was low expressed in the LAD patients and cells, associating with poor outcome. LINC00365 up-regulation attenuated H1975 cells proliferation, migration, invasion, glycolysis and in vivo growth. LINC00365 inhibited KCTD12 expression by sponging miR-429. miR-429 up-regulation and KCTD12 down-regulation partial reversed LINC00365 inhibition on H1975 cells malignant phenotype. Thus, LINC00365 inhibited LAD progression and glycolysis via targeting miR-429/KCTD12 axis. LINC00365 might be a potential candidate for LAD target treatment clinically.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

[Quantitative analysis of the effects of different stimuli on the contraction of gastrocnemius in vivo and in vitro specimen].

OBJECTIVE: To quantitatively analyze the effects of direct and indirect stimuli on the contraction of gastrocnemius in vivo and in vitro specimen by self-programming. METHODS: All specimens were divided into four groups: indirect stimuli on specimen in vivo group (n=12), direct stimuli on specimen in vivo group (n=8), indirect stimuli on specimen in vitro group (n=12), direct stimuli on specimen in vitro group (n=8). Indirect stimuli (via sciatic nerve) and direct stimuli (acupuncture needle piercing into gastrocnemius) (stimuli starting from 0 V, cycle 3 s, increment 0.02 V, 150 times) were acted on in vivo and in vitro sciatic nerve gastrocnemius muscle specimen respectively. The effects of electric intensity on the contraction of gastrocnemius were recorded by the experimental system of BL-420F. The data were processed and analyzed by the help of self-programming, to quantitatively obtain key parameters for a single contraction. RESULTS: ① For in vivo specimen, compared with direct stimuli, effects of indirect stimuli were as follows: the threshold intensity, half-intensity and maximal intensity of the specimen were smaller (P＜0.05); the amplitude was larger, the contraction period was longer, and the rising slope was smaller (P＜0.05). ②For in vitro specimen, compared with direct stimuli, effects of indirect stimuli were as follows: the threshold intensity, half-intensity and maximal intensity of indirect stimuli were smaller (P＜0.05); the amplitude was larger, the contraction period was longer, and the rising slope was smaller (P＜0.05). ③Compared with in vitro specimen, there was no significant difference among all the above parameters of in vivo specimen, with either direct or indirect stimuli (P＞0.05). CONCLUSION: There is no significant difference in the features of single contraction between in vivo and in vitro specimen with either direct or indirect stimuli. However, indirect stimuli can trigger gastrocnemius to produce single contraction more easily than direct stimuli, and the amplitude is larger than that of direct stimuli.

Effectiveness of fibrin sealant as a hemostatic technique in accelerating endoscopic submucosal dissection-induced ulcer healing and preventing stricture in the esophagus: A retrospective study.

The aim of the present retrospective study was to evaluate the effectiveness of conservative electrocoagulation followed by porcine fibrin sealant (FS) as a protective hemostatic technique for wounded microvessels in promoting the healing of endoscopic submucosal dissection (ESD)-induced ulcer, and preventing esophageal strictures that follow ESD. A total of 203 patients with early esophageal cancer or precancerous lesions were retrospectively analyzed. The 1-month ulcer healing and stricture rates were compared between the two groups (combined hemostats and electrocautery groups). The 1-month complete healing rate was 77.0% in the combined hemostats group and 52.6% in the electrocautery group (P=0.003). The use of FS and a smaller resected range (<3/4 circumference) was associated with a better 1-month healing rate. For patients with a ≥3/4 circumference mucosal defect, the esophageal stricture rate was 31.6% (6/19) in the combined hemostats group and 25.0% (2/8) in the electrocautery group. There was no difference in the stricture rate (P=0.737) and dilation time (P=0.733) between the two groups. In conclusion, the application of conservative electrocoagulation followed by porcine FS as a wound-protection technique promoted ESD-induced ulcer healing in the esophagus. However, this combined hemostatic technique was not superior to the conventional hemostatic method in preventing post-ESD stricture in patients with large esophageal mucosal defects.

Neoadjuvant Crizotinib in Resectable Locally Advanced Non-Small Cell Lung Cancer with ALK Rearrangement.

BACKGROUND: Locally advanced NSCLC is one of the most heterogeneous conditions, with multidimensional treatments involved. Neoadjuvant therapy had been commonly considered an optimal management strategy for patients with operable locally advanced. However, as targeted therapy has been widely applied in advanced NSCLC, neoadjuvant targeted therapy has remained poorly explored in locally advanced disease. METHODS: We have described 11 ALK receptor tyrosine kinase gene (ALK)-positive patients with pathologically confirmed N2 NSCLC who were treated with neoadjuvant crizotinib. All the patients were treatment naive and received crizotinib at a starting dose of 250 mg twice daily. Patient 3 was provided with dynamic monitoring before and after neoadjuvant therapy through next-generation sequencing of plasma and tissue. In case 4, next-generation sequencing of preoperative tissue was performed. RESULTS: Of the 11 patients, 10 had a partial response and one was stable disease after neoadjuvant crizotinib, with one suffering from grade 4 hepatic damage. Of the 11 patients, 10 (91.0%) received an R0 resection and 2 patients achieved a pathological complete response to neoadjuvant crizotinib. Six patients had disease recurrence, with five of them receiving crizotinib as first-line treatment and achieving a long duration of response. Dynamic monitoring of both plasma and tissue simultaneously indicated a decrease in sensitive ALK signaling in patient 3 and a partial response (approximately 50% of partial response), and no ALK-dependent resistance variants were captured. CONCLUSION: Neoadjuvant crizotinib may be feasible and well tolerated in locally advanced disease for complete resection. Crizotinib therapy before surgery may provide thorough elimination of circulating molecular residual disease and not influence the reuse of first-line crizotinib, but ongoing prospective trials are warranted to prove its efficacy in the neoadjuvant setting.

Efficient preparation of (R)-2-chloromandelic acid via a recycle process of resolution.

Efficient preparation of (R)-2-chloromandelic acid based on a recycle process of resolution is described. In the process, the desired was obtained by coordination-mediated resolution with D-O,O'-di-(p-toluoyl)-tartaric acid in the presence of Ca(2+) . Meanwhile, the undesired could be racemized in the presence of sodium hydroxide and the product was suitable for further resolution. A carbanion mechanism for the racemization of is proposed.

Evaluation of the 7th edition of the TNM classification in patients with resected esophageal squamous cell carcinoma.

AIM: To evaluate the prognostic factors and tumor stages of the 7(th) edition TNM classification for esophageal cancer. METHODS: In total, 1033 patients with esophageal squamous cell carcinoma (ESCC) who underwent surgical resection with or without (neo)adjuvant therapy between January 2003 and June 2012 at the Thoracic Surgery Department II of the Beijing Cancer Hospital, Beijing, China were included in this study. The following eligibility criteria were applied: (1) squamous cell carcinoma of the esophagus or gastroesophageal junction identified by histopathological examination; (2) treatment with esophagectomy plus lymphadenectomy with curative intent; and (3) complete pathologic reports and follow-up data. Patients who underwent non-curative (R1) resection and patients who died in hospital were excluded. Patients who received (neo)adjuvant therapy were also included in this analysis. All patients were restaged using the 7(th) edition of the Union for International Cancer Control and the American Joint Committee on Cancer TNM staging systems. Univariate and multivariate analyses were performed to identify the prognostic factors for survival. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between the subgroups. RESULTS: Of the 1033 patients, 273 patients received (neo)adjuvant therapy, and 760 patients were treated with surgery alone. The median follow-up time was 51.6 mo (range: 5-112 mo) and the overall 5-year survival rate was 36.4%. Gender, "pT" and "pN" descriptors, (neo)adjuvant therapy, and the 7(th) edition TNM stage grouping were independent prognostic factors in the univariate and multivariate analyses. However, neither histologic grade nor cancer location were independent prognostic factors in the univariate and multivariate analyses. The 5-year stage-based survival rates were as follows: IA, 84.9%; IB, 70.9%; IIA, 56.2%; IIB, 43.3%; IIIA, 37.9%; IIIB, 23.3%; IIIC,12.9% and IV, 3.4%. There were significant differences between each adjacent staging classification. Moreover, there were significant differences between each adjacent pN and pM subgroup. According to the pT descriptor, there were significant differences between each adjacent subgroup except between pT3 and pT4 (P = 0.405). However, there was no significant difference between each adjacent histologic grade subgroup and between each adjacent cancer location subgroup. CONCLUSION: The 7(th) edition is considered to be valid for patients with resected ESCC. However, the histologic grade and cancer location were not prognostic factors for ESCC.

[Diagnostic value of enhanced computed tomography plus vascular endothelial growth factor C expression in hilar and mediastinal lymph node metastasis of non-small cell lung cancer].

OBJECTIVE: To explore the diagnostic value of preoperative enhanced computed tomography (CT) plus vascular endothelial growth factor C (VEGF-C) expression in hilar and mediastinal lymph nodes metastasis of non-small cell lung cancer. METHODS: A total of 87 patients with non-small cell lung cancer (NSCLC) received preoperative chest enhanced CT scans and underwent standard radical operation and systematic lymph node dissection. Pathologic examination was selected as the gold standard to determine lymph node metastasis. The immunohistochemical method was used to detect the expression of VEGF-C. The predicting values of chest enhanced CT, VEGF-C expression and their combination for the diagnosis of hilar and mediastinal lymph nodes metastasis were evaluated through comparing the sensitivity, specificity and accuracy. RESULTS: The sensitivity of CT scan was 75.0%, specificity 59.6% and accuracy 66.7%. The positive expression rate of VEGF-C was 78.2% (68/87) and strong positive rate 13.8% (12/87). The sensitivity of VEGF-C was 97.5%, specificity 38.3% and accuracy 65.5%. The combination of CT and VEGF-C had a better accuracy (74.7%) and the sensitivity and specificity were 80.0% and 70.2% respectively. CONCLUSION: Compared with CT scan or VEGF-C expression alone, the combination of CT and VEGF-C improves the specificity and accuracy of diagnosing lymph nodes metastasis in NSCLC. If this combination method is employed before therapy, the accuracy of clinical nodal staging may be enhanced.