Anlotinib plus docetaxel vs. docetaxel alone for advanced non-small-cell lung cancer patients who failed first-line treatment: A multicenter, randomized phase II trial.

OBJECTIVES: Given the modest efficacy of docetaxel in advanced non-small cell lung cancer (NSCLC), this study assesses the therapeutic potential and safety profile of anlotinib in combination with docetaxel compared to docetaxel monotherapy as a second-line therapy for patients with advanced NSCLC. MATERIALS AND METHODS: In this phase II study, patients with advanced NSCLC experiencing failure with first-line platinum-based regimens were randomized in a 1:1 ratio to receive either anlotinib plus docetaxel or docetaxel alone. Primary endpoint was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety as secondary endpoints. RESULTS: A total of 83 patients were randomized. The combination of anlotinib and docetaxel significantly extended median PFS to 4.4 months compared to 1.6 months for docetaxel alone (hazard ratio [HR] = 0.38, 95 % confidence interval [CI]: 0.23-0.63, P = 0.0002), and also demonstrated superior ORR (32.5 % vs. 9.3 %, P = 0.0089) and DCR (87.5 % vs. 53.5 %, P = 0.0007). Median OS was observed at 12.0 months in the combination group vs. 10.9 months in the monotherapy group (HR = 0.82, 95 % CI: 0.47-1.43, P = 0.4803). For patients previously treated with immunotherapy, the median PFS was notably longer at 7.8 vs. 1.7 months (HR = 0.22, 95 % CI: 0.09-0.51, P = 0.0290). The incidence of grade ≥ 3 treatment-related adverse events, predominantly leukopenia (15.0 % vs. 7.0 %) and neutropenia (10.0 % vs. 5.0 %), was manageable across both groups. CONCLUSION: Anlotinib plus docetaxel offers a viable therapeutic alternative for patients with advanced NSCLC who failed first-line platinum-based treatments.

Serum Exosomes-Based Biomarker circ_0008928 Regulates Cisplatin Sensitivity, Tumor Progression, and Glycolysis Metabolism by miR-488/HK2 Axis in Cisplatin-Resistant Nonsmall Cell Lung Carcinoma.

Background: Nonsmall cell lung carcinoma (NSCLC) is a major cause of cancer-related death worldwide. The resistance of NSCLC to chemical drugs, such as cisplatin (CDDP), poses a heavy burden for NSCLC therapy. Herein, the effects of circular_0008928 (circ_0008928) on the CDDP sensitivity and biological behavior of CDDP-resistant NSCLC cells and underlying mechanism are revealed. Materials and Methods: The expression of circ_0008928 and microRNA-488 (miR-488) was detected by quantitative real-time polymerase chain reaction. The expression of hexokinase 2 (HK2) protein and exosome-specific proteins was determined by Western blot. The half-maximal inhibitory concentration (IC50) value of CDDP was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and migratory and invasive abilities were illustrated by cell counting kit-8 and transwell assays. Cell glycolysis metabolism was illustrated by extracellular acidification rate assay, glucose kit and lactate kit assays and Western blot analysis. The binding sites between miR-488 and circ_0008928 or HK2 were predicted by starbase or microT-CDS online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0008928 expression and HK2 protein expression were significantly upregulated, while miR-488 expression was obviously downregulated in NSCLC cells and CDDP-resistant NSCLC cells. Circ_0008928 expression was increased in serum exosomes of CDDP-resistant NSCLC patients compared with CDDP-sensitive NSCLC patients. In addition, circ_0008928 silencing improved CDDP sensitivity and attenuated CDDP-induced cell proliferation, migration, invasion, and glycolysis metabolism. Circ_0008928 was a sponge of miR-488, and miR-488 bound to HK2 in CDDP-resistant NSCLC cells. Furthermore, both miR-488 inhibitor and HK2 overexpression attenuated circ_0008928 absence-mediated impacts on CDDP sensitivity and tumor process in CDDP-resistant NSCLC. Conclusions: Circ_0008928 knockdown improved CDDP sensitivity and hindered cell proliferation, migration, invasion, and glycolysis metabolism by miR-488/HK2 axis in CDDP-resistant NSCLC. This finding provides a new mechanism for studying CDDP-resistant therapy in NSCLC.

[Morphologic and physiochemical properties of bovine jugular conduit stabilized by dye-mediated poto-oxidation].

OBJECTIVE: To determine the morphologic and physiochemical properties of bovine jugular conduit with valves stabilized by dye-mediated photo-oxidation. METHODS: Twenty-four bovine jugular conduits with valves were divided into 3 groups and treated with dye-mediated photo-oxidation (Group I), glutaraldehyde (Group II) and untreated group (Group II), respectively. Morphologic and physiochemical properties of the 3 groups, including wall thickness, diameter, tissue water content, heat shrinking temperature, breaching strength, and tissue protein extraction assay were studied. RESULTS: There was no difference in wall thickness, diameter, tissue water content, and heat shrinking temperature between Group I and II ,but there was significant difference between Group I and II. The breaching strength of Group I was higher than that of Group IU (P < 0.05), but lower than that of Group II (P < 0. 05). A decrease in extractable tissue protein was found in Group I and II. CONCLUSION: The dye-mediated photooxidation can effectively preserve the structure and the anti-regurgitation function of valves and improve the tissue stability and enhance the tension of bovine jugular conduit with valves.

[Expression of the heat shock protein-70 in the myocardial cells of cyanosis congenital heart diseases].

OBJECTIVE: To evaluate the expression and myocardial protection of heat shock protein-70 (HSP70) in the myocardial cells of cyanosis congenital heart diseases. METHODS: The study enrolled 24 patients with congenital heart disease: 12 cases of non-cyanosis (group A), and the other 12 cases of cyanosis (group B). During the operation the samples of myocardium in the right atrium were attained at 0 min ischemia, 20 min ischemia, and 20 min reperfusion. They were used to evaluate the content of HSP70 by immunohistochemistry and activation of SOD and content of MDA by chemochromatometry. RESULTS: The content of HSP70 in myocardial cells during the operation was not significantly different in both groups (P > 0. 05). The content of HSP70 significantly decreased in group B compared with that of group A (P <0.05). The activity of SOD significantly decreased and the content of MDA significantly increased in group B during the operation (P < 0.05). CONCLUSION: Decreased expression of HSP70 is associated with the decreased tolerance to ischemia-reperfusion injury in myocardial cells of cyanosis congenital heart disease.