Lung cancer immunochemotherapy: Codelivery of EGFR tki and PTX via an immunostimulatory dual functional nanocarrier.

e15177 Background: Immuno-target therapy combines a target therapy agent with an immune modulating agent and represents an attractive approach to improve cancer therapy.However, the success of it is hampered by the lack of a strategy to effectively co deliver the two therapeutics to the tumours.Here we report an improved dual functional nanocarrier (PEG5k-Fmoc-NLG2) to load Gefitinib for improved cancer Immuno target therapy.PEG5K-Fmoc-NLG2 is a prodrug that can inhibited IDO enzyme activity in vitro,while IDO1 inhibition reversed T cell suppression mediated by IDO expressing mouse cancer cells. Methods: Gefitinib loaded in carrier was prepared via a film hydrationmethod,the physicochemical properties of micelles was determined by TEM and particle size test.The cytotoxicity of the drug was detected by MTT assay. 3LL lung cancer was inoculated in mice and different drugs was injected through the tail vein to compare the anti tumor effect of drug loading micells with existing targeted drug gefitinib and CTLA4 antibody; tumor tissue proteins were extracted to clarify changes in pEGFR expressionexpression; flow cytometry will be finished to observe tumor immune microenvironment changes. Results: 1. Gefitinib loaded micelle maintain the similar size with blank PEG5k-fmoc-NLG2 micelles that is around 20nm.The drug-loaded micelles produced uniformed size and morphology. which further confirmed the size of micelles was around 20nm. 2. PTX and Gefitinib loaded in PEG5k-fmoc-NLG2 exhibited significantly enhanced tumor cell killing effect than the free drug on both A549 and 3LL cell lines. 3. The antitumor efficacy of different drugs loaded in the carrier were tested in a murine lung cancer model (3LL). All treatment showed significant better antitumor activity compared to the control group, Gefitinib/PEG5k-Fmoc-NLG2 plus CTLA4 antibody exhibited the best antitumor effect. Antitumor activity of gefitinib loaded in carrier was comparable with free gefitinib alone. 4. With various treatments the expression of p-EGFR protein level varied. Basically, compare with free gefitinib alone, the carrier loaded gefitinib was more effective in the inhibition of EGFR phosphorylation. Conclusions: We have shown that targeted delivery of PTX and Gefitinib via a immunostimulatory nanocarrier effectively improved drugs antitumor activity. More study about tumor immune microenvironment are required. Such strategy can be employed in novel therapy combining chemotherapy drugs and immunemodulating agents such as PD-1 and CTLA4. </jats:p

Increased Level of Annexin A1 in Bronchoalveolar Lavage Fluid as a Potential Diagnostic Indicator for Lung Cancer

Background Annexin A1 has been implicated in various tumor types, but few studies have investigated its involvement in lung cancer. The purpose of this investigation was to quantify the annexin A1 level in bronchoalveolar lavage fluid (BALF) and analyze its usefulness in lung cancer diagnosis. Methods Annexin A1 expression was measured by immunohistochemistry and enzyme immunoassay. The sensitivity and specificity of annexin A1 for distinguishing lung cancer were determined by receiver operator characteristic (ROC) curves. Results Tumor tissues, BALF and serum of patients with lung cancer contained higher levels of annexin A1 than those of the control group of patients with benign lung diseases. Moreover, an increased level of BALF annexin A1 was closely correlated with lymphatic invasion and malignant progression of lung cancer. The sensitivity and specificity of BALF annexin A1 for distinguishing lung cancer were 94.2% and 90.2%, respectively. Conclusions Increased annexin A1 in BALF was correlated with lymphatic invasion and malignant progression of lung cancer, suggesting that it could be an indicator for discerning lung cancer and predicting outcome. </jats:sec

Trends, Symptoms, and Outcomes of Resectable Giant Mediastinal Tumors

Describing the changes in surgical procedures and factors affecting the surgical outcome of patients who have undergone complete resection of giant mediastinal tumors (GMTs, diameter ≥ 10 centimeters) could improve preoperative decision-making and prognostic evaluations. We accessed data from three sources, which are case reports on surgical treatment of GMTs from PubMed, Web of Science, and EMBASE until June 1, 2019; patients with resected GMT from the Surveillance, Epidemiology, and End Results (SEER) database; and retrospective review of medical records in our institution from 2000 to 2019. The worldwide distribution, clinicopathological characteristics, symptom profile, prognosis of patients with GMT resection, and nomogram for surgical outcome prediction are reported. A total of 242 rare GMT cases from four continents (Asia, North America, South America, and Europe) were included. The median age of the patients was 40 (IQR: 27, range: 13–83) years, and the male-to-female ratio was 1.57:1. Dyspnea, shortness of breath, cough, and chest pain or discomfort were the major symptoms at presentation. The prognosis of benign and low-grade malignant GMTs was superior to that of high-grade malignant GMTs. Tumor malignancy played the most critical role in predicting postoperative survival, followed by longest tumor diameter and a posterior mediastinum location. The findings of this study suggest that the number of successful GMT surgeries has increased over the last decade and describe clinical features of GMTs. Physicians should prioritize tumor malignancy as a leading factor in predicting outcome rather than tumor size.</jats:p